Editing Neurotransmitter

{{short description|Chemical substance that enables neurotransmission}}
{{For|an introduction to concepts and terminology used in this article|Chemical synapse}}
{{Use dmy dates|date=June 2018}}
{{Synapse map}}

A '''neurotransmitter''' is a [[signaling molecule]] secreted by a [[neuron]] to affect another cell across a [[Chemical synapse|synapse]]. The cell receiving the signal, or target cell, may be another neuron, but could also be a [[gland]] or [[muscle cell]].<ref>{{Cite book |last1=Smelser |first1=Neil J. |title=International encyclopedia of the social & behavioral sciences |last2=Baltes |first2=Paul B. |date=2001 |publisher=Elsevier |isbn=978-0-08-043076-8 |edition=1st |location=Amsterdam New York}}</ref>

Neurotransmitters are released from [[synaptic vesicles]] into the [[synaptic cleft]] where they are able to interact with [[neurotransmitter receptor]]s on the target cell. Some neurotransmitters are also stored in [[large dense core vesicles]].<ref>{{Cite journal |last=Edwards |first=Robert H |date=December 1998 |title=Neurotransmitter release: Variations on a theme |url=https://linkinghub.elsevier.com/retrieve/pii/S0960982207005519 |journal=Current Biology |volume=8 |issue=24 |pages=R883–R885 |doi=10.1016/s0960-9822(07)00551-9 |pmid=9843673 |bibcode=1998CBio....8.R883E |issn=0960-9822}}</ref> The neurotransmitter's effect on the target cell is determined by the receptor it binds to. Many neurotransmitters are synthesized from simple and plentiful precursors such as [[amino acid]]s, which are readily available and often require a small number of [[biosynthetic]] steps for conversion.{{cn|date=March 2025}}

Neurotransmitters are essential to the function of complex neural systems. The exact number of unique neurotransmitters in humans is unknown, but more than 100 have been identified.<ref>{{cite book | vauthors = Cuevas J | chapter = Neurotransmitters and Their Life Cycle |date=2019-01-01 | title =Reference Module in Biomedical Sciences |publisher=Elsevier |doi=10.1016/b978-0-12-801238-3.11318-2 |isbn=978-0-12-801238-3 }}</ref> Common neurotransmitters include [[Glutamate (neurotransmitter)|glutamate]], [[GABA]], [[acetylcholine]], [[glycine]], [[dopamine]] and [[norepinephrine]].

==Mechanism and cycle==
{{See also|Neurotransmission}}

===Synthesis===

Neurotransmitters are generally synthesized in neurons and are made up of, or derived from, precursor molecules that are found abundantly in the cell. Classes of neurotransmitters include [[amino acid]]s, [[monoamines]], and [[peptide]]s. Monoamines are synthesized by altering a single amino acid. For example, the precursor of serotonin is the amino acid tryptophan. Peptide neurotransmitters, or [[neuropeptide]]s, are protein transmitters which are larger than the classical small-molecule neurotransmitters and are often released together to elicit a modulatory effect.<ref>{{Cite book | vauthors = Purves D, Augustine GJ, Fitzpatrick D, Katz LC, LaMantia AS, McNamara JO, Williams SM |date=2001| chapter = Peptide Neurotransmitters | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK10873/ | title = Neuroscience |publisher=Sinauer Associates | edition = 2nd }}</ref> Purine neurotransmitters, like [[Adenosine triphosphate|ATP]], are derived from nucleic acids. Metabolic products such as [[nitric oxide]] and [[carbon monoxide]] have also been reported to act like neurotransmitters.<ref>{{Cite journal |last1=Xue |first1=L. |last2=Farrugia |first2=G. |last3=Miller |first3=S. M. |last4=Ferris |first4=C. D. |last5=Snyder |first5=S. H. |last6=Szurszewski |first6=J. H. |date=2000-02-15 |title=Carbon monoxide and nitric oxide as coneurotransmitters in the enteric nervous system: Evidence from genomic deletion of biosynthetic enzymes |journal=Proceedings of the National Academy of Sciences |language=en |volume=97 |issue=4 |pages=1851–1855 |doi=10.1073/pnas.97.4.1851 |doi-access=free |issn=0027-8424 |pmc=26525 |pmid=10677545|bibcode=2000PNAS...97.1851X }}</ref>
{| class="wikitable"
!
!Examples
|-
|Amino acids
|[[glycine]], [[glutamate]]
|-
|Monoamines
|[[serotonin]], [[epinephrine]], [[dopamine]]
|-
|Peptides
|[[substance P]], [[opioid]]s
|-
|Purines
|[[Adenosine triphosphate|ATP]], [[Guanosine triphosphate|GTP]]
|-
|Other
|[[nitric oxide]], [[carbon monoxide]]
|}

===Storage===

[[File:Neurotransmitters.jpg|thumb|Synaptic vesicles containing neurotransmitters]]
Neurotransmitters are generally stored in [[synaptic vesicles]], clustered close to the [[cell membrane]] at the [[axon terminal]] of the presynaptic neuron. However, some neurotransmitters, like the metabolic gases carbon monoxide and nitric oxide, are synthesized and released immediately following an action potential without ever being stored in vesicles.<ref>{{cite journal | vauthors = Sanders KM, Ward SM | title = Nitric oxide and its role as a non-adrenergic, non-cholinergic inhibitory neurotransmitter in the gastrointestinal tract | journal = British Journal of Pharmacology | volume = 176 | issue = 2 | pages = 212–227 | date = January 2019 | pmid = 30063800 | pmc = 6295421 | doi = 10.1111/bph.14459 }}</ref>

===Release===

Generally, a neurotransmitter is released via [[exocytosis]] at the presynaptic terminal in response to an electrical signal called an [[action potential]] in the presynaptic neuron. However, low-level "baseline" release also occurs without electrical stimulation. Neurotransmitters are released into and diffuse across the [[synaptic cleft]], where they bind to specific [[Receptor (biochemistry)|receptors]] on the membrane of the postsynaptic neuron.<ref>{{cite book | vauthors = Elias LJ, Saucier DM | date =2005 | title = Neuropsychology: Clinical and Experimental Foundations. | location = Boston | publisher = Pearson }}</ref>

===Receptor interaction===

After being released into the synaptic cleft, neurotransmitters diffuse across the synapse where they are able to interact with receptors on the target cell. The effect of the neurotransmitter is dependent on the identity of the target cell's receptors present at the synapse. Depending on the receptor, binding of neurotransmitters may cause [[Excitatory synapse|excitation]], [[Inhibitory postsynaptic potential|inhibition]], or modulation of the postsynaptic neuron.<ref name=":1" />

===Elimination===
[[File:Synapse acetylcholine.png|thumb|Acetylcholine is cleaved in the synaptic cleft into acetic acid and choline.]]

In order to avoid continuous activation of receptors on the post-synaptic or target cell, neurotransmitters must be removed from the synaptic cleft.<ref>{{cite journal | vauthors = Chergui K, Suaud-Chagny MF, Gonon F | title = Nonlinear relationship between impulse flow, dopamine release and dopamine elimination in the rat brain in vivo | journal = Neuroscience | volume = 62 | issue = 3 | pages = 641–645 | date = October 1994 | pmid = 7870295 | doi = 10.1016/0306-4522(94)90465-0 | s2cid = 20465561 }}</ref>  Neurotransmitters are removed through one of three mechanisms:

# Diffusion – neurotransmitters drift out of the synaptic cleft, where they are absorbed by [[glial cells]]. These glial cells, usually [[astrocyte]]s, absorb the excess neurotransmitters.
#* Astrocytes, a type of [[glia]]l cell in the brain, actively contribute to synaptic communication through astrocytic diffusion or [[Gliotransmitter|gliotransmission]]. Neuronal activity triggers an increase in astrocytic calcium levels, prompting the release of gliotransmitters, such as [[Glutamate (neurotransmitter)|glutamate]], ATP, and D-serine. These gliotransmitters diffuse into the [[Extracellular fluid|extracellular]] space, interacting with nearby neurons and influencing synaptic transmission. By regulating extracellular neurotransmitter levels, astrocytes help maintain proper synaptic function. This bidirectional communication between astrocytes and neurons add complexity to brain signaling, with implications for brain function and neurological disorders.<ref>{{Cite journal |last1=Mustafa |first1=Asif K. |last2=Kim |first2=Paul M. |last3=Snyder |first3=Solomon H. |date=August 2004 |title=D-Serine as a putative glial neurotransmitter |journal=Neuron Glia Biology |language=en |volume=1 |issue=3 |pages=275–281 |doi=10.1017/S1740925X05000141 |pmid=16543946 |pmc=1403160 |issn=1741-0533}}</ref><ref>{{Cite journal |last1=Wolosker |first1=Herman |last2=Dumin |first2=Elena |last3=Balan |first3=Livia |last4=Foltyn |first4=Veronika N. |date=July 2008 |title=d-Amino acids in the brain: d-serine in neurotransmission and neurodegeneration: d-Serine in neurotransmission and neurodegeneration |journal=FEBS Journal |language=en |volume=275 |issue=14 |pages=3514–3526 |doi=10.1111/j.1742-4658.2008.06515.x|pmid=18564180 |s2cid=25735605 |doi-access=free }}</ref>
# Enzyme degradation – proteins called [[enzymes]] break the neurotransmitters down.
# [[Reuptake]] – neurotransmitters are reabsorbed into the pre-synaptic neuron. Transporters, or [[membrane transport protein]]s, pump neurotransmitters from the synaptic cleft back into [[axon terminal]]s (the presynaptic neuron) where they are stored for reuse.

For example, [[acetylcholine]] is eliminated by having its acetyl group cleaved by the enzyme [[acetylcholinesterase]]; the remaining [[choline]] is then taken in and recycled by the pre-synaptic neuron to synthesize more [[acetylcholine]].<ref>{{cite journal | vauthors = Thapa S, Lv M, Xu H | title = Acetylcholinesterase: A Primary Target for Drugs and Insecticides | journal = Mini Reviews in Medicinal Chemistry | volume = 17 | issue = 17 | pages = 1665–1676 | date = 2017-11-30 | pmid = 28117022 | doi = 10.2174/1389557517666170120153930 }}</ref> Other neurotransmitters are able to [[Diffusion|diffuse]] away from their targeted synaptic junctions and are eliminated from the body via the kidneys, or destroyed in the liver. Each neurotransmitter has very specific degradation pathways at regulatory points, which may be targeted by the body's regulatory system or medication. [[Cocaine]] blocks a dopamine transporter responsible for the reuptake of dopamine. Without the transporter, dopamine diffuses much more slowly from the synaptic cleft and continues to activate the dopamine receptors on the target cell.<ref>{{cite journal | vauthors = Vasica G, Tennant CC | title = Cocaine use and cardiovascular complications | journal = The Medical Journal of Australia | volume = 177 | issue = 5 | pages = 260–262 | date = September 2002 | pmid = 12197823 | doi = 10.5694/j.1326-5377.2002.tb04761.x | s2cid = 18572638 }}</ref>

==Discovery==
{{see also|History of catecholamine research}}
Until the early 20th century, scientists assumed that the majority of synaptic communication in the brain was electrical. However, through [[Histology|histological]] examinations by [[Ramón y Cajal]], a 20 to 40&nbsp;nm gap between neurons, known today as the [[synaptic cleft]], was discovered. The presence of such a gap suggested communication via chemical messengers traversing the synaptic cleft, and in 1921 German pharmacologist [[Otto Loewi]] confirmed that neurons can communicate by releasing chemicals. Through a series of experiments involving the vagus nerves of frogs, Loewi was able to manually slow the heart rate of frogs by controlling the amount of saline solution present around the vagus nerve. Upon completion of this experiment, Loewi asserted that sympathetic regulation of cardiac function can be mediated through changes in chemical concentrations. Furthermore, Otto Loewi is credited with discovering [[acetylcholine]] (ACh) – the first known neurotransmitter.<ref>Saladin, Kenneth S. ''Anatomy and Physiology: The Unity of Form and Function''. McGraw Hill. 2009 {{ISBN|0-07-727620-5}}</ref>

==Identification==
To identify neurotransmitters, the following criteria are typically considered:
# Synthesis: The chemical must be produced within the neuron or be present in it as a precursor molecule.
# Release and response: When the neuron is activated, the chemical must be released and elicit a response in target cells or neurons.
# Experimental response: Application of the chemical directly to the target cells should produce the same response observed when the chemical is naturally released from neurons.
# Removal mechanism: There must be a mechanism in place to remove the neurotransmitter from its site of action once its signaling role is complete.<ref>{{Cite journal |last1=Teleanu |first1=Raluca Ioana |last2=Niculescu |first2=Adelina-Gabriela |last3=Roza |first3=Eugenia |last4=Vladâcenco |first4=Oana |last5=Grumezescu |first5=Alexandru Mihai |last6=Teleanu |first6=Daniel Mihai |date=2022-05-25 |title=Neurotransmitters—Key Factors in Neurological and Neurodegenerative Disorders of the Central Nervous System |journal=International Journal of Molecular Sciences |language=en |volume=23 |issue=11 |pages=5954 |doi=10.3390/ijms23115954 |issn=1422-0067 |pmc=9180936 |pmid=35682631 |doi-access=free }}</ref>

However, given advances in [[pharmacology]], [[genetics]], and chemical [[neuroanatomy]], the term "neurotransmitter" can be applied to chemicals that:
* Carry messages between neurons via influence on the postsynaptic membrane.
* Have little or no effect on membrane voltage, but have a common carrying function such as changing the structure of the synapse.
* Communicate by sending reverse-direction messages that affect the release or [[reuptake]] of transmitters.

The anatomical localization of neurotransmitters is typically determined using [[Immunocytochemistry|immunocytochemical]] techniques, which identify the location of either the transmitter substances themselves or of the enzymes that are involved in their synthesis. Immunocytochemical techniques have also revealed that many transmitters, particularly the [[neuropeptide]]s, are co-localized, that is, a neuron may release more than one transmitter from its [[synaptic terminal]].<ref name="BioPsych Breedlove & Watson">{{cite book| vauthors = Breedlove SM, Watson NV |author1-link=Marc Breedlove|title=Biological psychology : an introduction to behavioral, cognitive, and clinical neuroscience|date=2013|publisher=Sinauer Associates|location=Sunderland, MA|isbn=978-0878939275|edition=Seventh}}</ref> Various techniques and experiments such as [[staining]], stimulating, and collecting can be used to identify neurotransmitters throughout the [[central nervous system]].<ref name="Kolb Intro to Brain & Behavior">{{cite book| vauthors = Whishaw B, Kolb IQ |title=An introduction to brain and behavior|date=2014|publisher=Worth Publishers|location=New York, NY|isbn=978-1429242288|pages=150–151|edition=4th}}</ref>

== Actions ==
Neurons communicate with each other through [[synapse]]s, specialized contact points where neurotransmitters transmit signals. When an [[action potential]] reaches the [[presynaptic terminal]], the action potential can trigger the release of neurotransmitters into the synaptic cleft. These neurotransmitters then bind to receptors on the postsynaptic membrane, influencing the receiving neuron in either an [[Inhibitory postsynaptic potential|inhibitory]] or [[Excitatory postsynaptic potential|excitatory]] manner. If the overall excitatory influences outweigh the inhibitory influences, the receiving neuron may generate its own action potential, continuing the transmission of information to the next neuron in the network. This process allows for the flow of information and the formation of complex neural networks.<ref>{{Citation |last1=Purves |first1=Dale |title=Excitatory and Inhibitory Postsynaptic Potentials |date=2001 |url=https://www.ncbi.nlm.nih.gov/books/NBK11117/ |work=Neuroscience. 2nd edition |access-date=2023-07-14 |publisher=Sinauer Associates |language=en |last2=Augustine |first2=George J. |last3=Fitzpatrick |first3=David |last4=Katz |first4=Lawrence C. |last5=LaMantia |first5=Anthony-Samuel |last6=McNamara |first6=James O. |last7=Williams |first7=S. Mark}}</ref>

===Modulation===
A neurotransmitter may have an excitatory, inhibitory or modulatory effect on the target cell. The effect is determined by the receptors the neurotransmitter interacts with at the post-synaptic membrane. Neurotransmitter influences trans-membrane ion flow either to increase (excitatory) or to decrease (inhibitory) the probability that the cell with which it comes in contact will produce an action potential. Synapses containing receptors with excitatory effects are called Type I synapses, while Type II synapses contain receptors with inhibitory effects.<ref>{{cite journal | vauthors = Peters A, Palay SL | title = The morphology of synapses | journal = Journal of Neurocytology | volume = 25 | issue = 12 | pages = 687–700 | date = December 1996 | pmid = 9023718 | doi = 10.1007/BF02284835 | s2cid = 29365393 }}</ref> Thus, despite the wide variety of synapses, they all convey messages of only these two types. The two types are different appearance and are primarily located on different parts of the neurons under its influence.<ref>{{Cite book|url=https://www.worldcat.org/oclc/881146319|title=Hole's human anatomy & physiology|vauthors=Shier D, Butler J, Lewis R|date=5 January 2015|isbn=978-0-07-802429-0|edition=Fourteenth|location=New York, NY|oclc=881146319}}</ref> Receptors with modulatory effects are spread throughout all synaptic membranes and binding of neurotransmitters sets in motion signaling cascades that help the cell regulate its function.<ref name=":1">{{cite journal | vauthors = Di Chiara G, Morelli M, Consolo S | title = Modulatory functions of neurotransmitters in the striatum: ACh/dopamine/NMDA interactions | journal = Trends in Neurosciences | volume = 17 | issue = 6 | pages = 228–233 | date = June 1994 | pmid = 7521083 | doi = 10.1016/0166-2236(94)90005-1 | s2cid = 32085555 }}</ref> Binding of neurotransmitters to receptors with modulatory effects can have many results. For example, it may result in an increase or decrease in sensitivity to future stimulus by recruiting more or less receptors to the synaptic membrane.{{cn|date=January 2025}}

Type I (excitatory) synapses are typically located on the shafts or the spines of dendrites, whereas type II (inhibitory) synapses are typically located on a cell body. In addition, Type I synapses have round synaptic vesicles, whereas the vesicles of type II synapses are flattened. The material on the presynaptic and post-synaptic membranes is denser in a Type I synapse than it is in a Type II, and the Type I synaptic cleft is wider. Finally, the active zone on a Type I synapse is larger than that on a Type II synapse.{{cn|date=January 2025}}

The different locations of Type I and Type II synapses divide a neuron into two zones: an excitatory dendritic tree and an inhibitory cell body. From an inhibitory perspective, excitation comes in over the dendrites and spreads to the [[axon hillock]] to trigger an [[action potential]]. If the message is to be stopped, it is best stopped by applying inhibition on the cell body, close to the axon hillock where the action potential originates. Another way to conceptualize excitatory–inhibitory interaction is to picture excitation overcoming inhibition. If the cell body is normally in an inhibited state, the only way to generate an action potential at the axon hillock is to reduce the cell body's inhibition. In this "open the gates" strategy, the excitatory message is like a racehorse ready to run down the track, but first, the inhibitory starting gate must be removed.<ref name="Kolb Intro to Brain and Behavior">{{cite book|title=An introduction to brain and behavior|vauthors=Whishaw B, Kolb IQ|date=2014|publisher=Worth Publishers|isbn=978-1429242288|edition=4th|location=New York, NY}}</ref>

===Neurotransmitter actions===
As explained above, the only direct action of a neurotransmitter is to activate a receptor. Therefore, the effects of a neurotransmitter system depend on the connections of the neurons that use the transmitter, and the chemical properties of the receptors.
* [[Glutamate (neurotransmitter)|Glutamate]] is used at the great majority of fast excitatory synapses in the brain and spinal cord. It is also used at most synapses that are "modifiable", i.e. capable of increasing or decreasing in strength. [[Synaptic plasticity|Modifiable synapses]] are thought to be the main memory-storage elements in the brain. Excessive glutamate release can overstimulate the brain and lead to [[excitotoxicity]] causing cell death resulting in seizures or strokes.<ref>{{cite journal|vauthors=Gross L|date=November 2006|title="Supporting" players take the lead in protecting the overstimulated brain|journal=PLOS Biology|volume=4|issue=11|pages=e371|doi=10.1371/journal.pbio.0040371|pmc=1609133|pmid=20076484 |doi-access=free }}</ref> Excitotoxicity has been implicated in certain chronic diseases including [[ischemic stroke]], [[epilepsy]], [[amyotrophic lateral sclerosis]], [[Alzheimer's disease]], [[Huntington disease]], and [[Parkinson's disease]].<ref name="pmid21729715">{{cite journal|vauthors=Yang JL, Sykora P, Wilson DM, Mattson MP, Bohr VA|date=August 2011|title=The excitatory neurotransmitter glutamate stimulates DNA repair to increase neuronal resiliency|journal=Mechanisms of Ageing and Development|volume=132|issue=8–9|pages=405–11|doi=10.1016/j.mad.2011.06.005|pmc=3367503|pmid=21729715}}</ref>
* [[GABA]] is used at the great majority of fast inhibitory synapses in virtually every part of the brain. Many [[sedative|sedative/tranquilizing drugs]] act by enhancing the effects of GABA.<ref>[http://www.sleepfoundation.org/article/orexin-receptor-antagonists-new-class-sleeping-pill Orexin receptor antagonists a new class of sleeping pill], National Sleep Foundation.</ref>
* [[Glycine]] is the primary inhibitory neurotransmitter in the [[spinal cord]].<ref>{{Cite journal |last1=Rajendra |first1=Sundran |last2=Lynch |first2=Joseph W. |last3=Schofield |first3=Peter R. |date=January 1997 |title=The glycine receptor |url=https://linkinghub.elsevier.com/retrieve/pii/S0163725896001635 |journal=Pharmacology & Therapeutics |language=en |volume=73 |issue=2 |pages=121–146 |doi=10.1016/S0163-7258(96)00163-5|pmid=9131721 |url-access=subscription }}</ref>
* [[Acetylcholine]] was the first neurotransmitter discovered in the peripheral and central nervous systems. It activates skeletal muscles in the somatic nervous system and may either excite or inhibit internal organs in the autonomic system.<ref name="Kolb Intro to Brain & Behavior" /> It is main neurotransmitter at the [[neuromuscular junction]] connecting motor nerves to muscles. The paralytic arrow-poison [[curare]] acts by blocking transmission at these synapses. Acetylcholine also operates in many regions of the brain as a [[Neuromodulation|neuromodulatory]], but using [[Acetylcholine receptor#Receptor types|different types of receptors]], including [[Nicotinic acetylcholine receptor|nicotinic]] and [[Muscarinic acetylcholine receptor|muscarinic]] receptors.<ref>{{cite web|title=Acetylcholine Receptors|url=http://www.ebi.ac.uk/interpro/potm/2005_11/Page2.htm|access-date=25 August 2014|publisher=Ebi.ac.uk}}</ref>
* [[Dopamine]] has a number of important functions in the brain. This includes critical role in the [[reward system]], motivation and emotional arousal. It also plays an important role in fine motor control and [[Parkinson's disease]] has been linked to low levels of dopamine due to the loss of [[dopaminergic neurons]] in [[substantia nigra]] [[pars compacta]].<ref>{{Citation |last1=Fahn |first1=Stanley |title=Chapter 3 - Functional neuroanatomy of the basal ganglia |date=2011-01-01 |work=Principles and Practice of Movement Disorders (Second Edition) |pages=55–65 |editor-last=Fahn |editor-first=Stanley |url=https://linkinghub.elsevier.com/retrieve/pii/B9781437723694000032 |access-date=2024-11-25 |place=Edinburgh |publisher=W.B. Saunders |doi=10.1016/b978-1-4377-2369-4.00003-2 |isbn=978-1-4377-2369-4 |last2=Jankovic |first2=Joseph |last3=Hallett |first3=Mark |editor2-last=Jankovic |editor2-first=Joseph |editor3-last=Hallett |editor3-first=Mark|url-access=subscription }}</ref> [[Schizophrenia]], a highly heterogeneous and complicated disorder has been linked to high levels of dopamine.<ref>Schacter, Gilbert and Weger. Psychology.United States of America.2009.Print.</ref>
* [[Serotonin]] is a [[monoamine neurotransmitter]]. Most of it is produced by the intestine (approximately 90%),<ref>{{Citation |last1=Terry |first1=Natalie |title=Serotonergic Mechanisms Regulating the GI Tract: Experimental Evidence and Therapeutic Relevance |date=2017 |work=Gastrointestinal Pharmacology |pages=319–342 |editor-last=Greenwood-Van Meerveld |editor-first=Beverley |place=Cham |publisher=Springer International Publishing |language=en |doi=10.1007/164_2016_103 |isbn=978-3-319-56360-2 |pmc=5526216 |pmid=28035530 |last2=Margolis |first2=Kara Gross|volume=239 }}</ref> and the remainder by [[central nervous system]] neurons at the [[raphe nuclei]]. It functions to regulate appetite, sleep, memory and learning, temperature, mood, behaviour, muscle contraction, and the functions of the [[cardiovascular system]] and [[endocrine system]]. It is speculated to have a role in [[Depression (mood)|depression]], as some depressed patients have been reported to exhibit lower concentrations of metabolites of serotonin in their [[cerebrospinal fluid]] and brain tissue.<ref name="serotonin">{{cite web|author=University of Bristol|title=Introduction to Serotonin|url=http://www.chm.bris.ac.uk/motm/serotonin/depression.htm|access-date=15 October 2009}}</ref>
* [[Norepinephrine]] is a member of the [[catecholamine]] family of neurotransmitters. It is synthesized from the [[amino acid]] [[tyrosine]]. In the [[peripheral nervous system]], one of the primary roles of norepinephrine is to stimulate the release of the stress hormone [[epinephrine]] (i.e. [[adrenaline]]) from the [[adrenal gland]]s.<ref name=":0">{{Citation |last1=Sheffler |first1=Zachary M. |title=Physiology, Neurotransmitters |date=2023 |url=http://www.ncbi.nlm.nih.gov/books/NBK539894/ |work=StatPearls |access-date=2023-07-16 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30969716 |last2=Reddy |first2=Vamsi |last3=Pillarisetty |first3=Leela Sharath}}</ref> Norepinephrine is involved in the [[fight-or-flight response]]<ref>{{Cite journal |last=Fitzgerald |first=P. J. |date=April 2015 |title=Noradrenaline transmission reducing drugs may protect against a broad range of diseases. |url=https://onlinelibrary.wiley.com/doi/10.1111/aap.12019 |journal=Autonomic and Autacoid Pharmacology |language=en |volume=34 |issue=3–4 |pages=15–26 |doi=10.1111/aap.12019 |pmid=25271382 |issn=1474-8665|url-access=subscription }}</ref> and is also affected in [[anxiety disorder]]s<ref>{{Cite journal |last1=Bouras |first1=Nadia N. |last2=Mack |first2=Nancy R. |last3=Gao |first3=Wen-Jun |date=2023-04-17 |title=Prefrontal modulation of anxiety through a lens of noradrenergic signaling |journal=Frontiers in Systems Neuroscience |language=English |volume=17 |doi=10.3389/fnsys.2023.1173326 |doi-access=free |issn=1662-5137 |pmc=10149815 |pmid=37139472}}</ref>  and depression.<ref>{{Cite journal |last1=Moret |first1=Chantal |last2=Briley |first2=Mike |date=2011-05-31 |title=The importance of norepinephrine in depression |journal=Neuropsychiatric Disease and Treatment |language=English |volume=7 |issue=Supplement 1 |pages=9–13 |doi=10.2147/NDT.S19619 |doi-access=free |pmc=3131098 |pmid=21750623}}</ref>
* [[Epinephrine]], a neurotransmitter and [[hormone]] is synthesized from [[tyrosine]]. It is released from the [[adrenal gland]]s and also plays a role in the fight-or-flight response. Epinephrine has [[Vasoconstriction|vasoconstrictive]] effects, which promote increased heart rate, blood pressure, energy mobilization. Vasoconstriction influences [[metabolism]] by promoting the breakdown of [[glucose]] released into the bloodstream. Epinephrine also has [[Bronchodilator|bronchodilation]] effects, which is the relaxing of airways.<ref name=":0" />

== Types ==
There are many different ways to classify neurotransmitters. They are commonly classified into [[amino acids]], [[monoamine]]s and [[peptides]].<ref>{{Cite book| vauthors = Prasad BV |title=Examining Biological Foundations of Human Behavior|publisher=IGI Global|year=2020|isbn=978-1799-8286-17|location=United States of America|pages=81}}</ref>

Some of the major neurotransmitters are:
* '''[[Amino acid]]s:''' [[glutamate]],<ref name="twsNovK11">{{cite news| vauthors = Sapolsky R |title=Biology and Human Behavior: The Neurological Origins of Individuality, 2nd |publisher=The Teaching Company|year=2005|quote=see pages 13 & 14 of Guide Book}}</ref> [[aspartate]], [[D-serine]], [[gamma-Aminobutyric acid]] (GABA),{{refn|group=nb|GABA is a ''non-proteinogenic'' amino acid}} [[glycine]]
* '''[[Gasotransmitter]]s:''' [[nitric oxide]] (NO), [[carbon monoxide]] (CO), [[hydrogen sulfide]] (H<sub>2</sub>S)
* '''[[Monoamine]]s:'''
** [[Catecholamine|'''Catecholamines''']]: [[dopamine]] (DA), [[norepinephrine]] (noradrenaline, NE), [[Adrenaline|epinephrine]] (adrenaline)
** '''[[Indolamines]]''': [[serotonin]] (5-HT, SER), [[melatonin]]
** [[histamine]]
* '''[[Trace amine]]s''': [[phenethylamine]], [[N-methylphenethylamine|''N''-methylphenethylamine]], [[tyramine]], [[3-iodothyronamine]], [[octopamine]], [[tryptamine]], etc.
* '''[[Peptide]]s:''' [[oxytocin]], [[somatostatin]], [[substance P]], [[cocaine and amphetamine regulated transcript]], [[opioid peptide]]s<ref name="pmid38738">{{cite journal | vauthors = Snyder SH, Innis RB | title = Peptide neurotransmitters | journal = Annual Review of Biochemistry | volume = 48 | pages = 755–82 | year = 1979 | pmid = 38738 | doi = 10.1146/annurev.bi.48.070179.003543 }}</ref>
* '''[[Purinergic signalling|Purines]]:''' [[adenosine triphosphate]] (ATP), [[adenosine]]
* Others: [[acetylcholine]] (ACh), [[anandamide]], etc.

In addition, over 100 neuroactive [[peptide]]s have been found, and new ones are discovered regularly.<ref>{{cite journal | vauthors = Corbière A, Vaudry H, Chan P, Walet-Balieu ML, Lecroq T, Lefebvre A, Pineau C, Vaudry D | display-authors = 6 | title = Strategies for the Identification of Bioactive Neuropeptides in Vertebrates | journal = Frontiers in Neuroscience | volume = 13 | pages = 948 | date = 18 September 2019 | pmid = 31619945 | pmc = 6759750 | doi = 10.3389/fnins.2019.00948 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Fricker LD, Devi LA | title = Orphan neuropeptides and receptors: Novel therapeutic targets | journal = Pharmacology & Therapeutics | volume = 185 | pages = 26–33 | date = May 2018 | pmid = 29174650 | pmc = 5899030 | doi = 10.1016/j.pharmthera.2017.11.006 }}</ref> Many of these are co-released along with a small-molecule transmitter. Nevertheless, in some cases, a peptide is the primary transmitter at a synapse. [[Beta-Endorphin]] is a relatively well-known example of a peptide neurotransmitter because it engages in highly specific interactions with [[opioid receptors]] in the [[central nervous system]].{{cn|date=January 2025}}

Single [[ions]] (such as synaptically released [[zinc]]) are also considered neurotransmitters by some,<ref>{{cite journal | vauthors = Kodirov SA, Takizawa S, Joseph J, Kandel ER, Shumyatsky GP, Bolshakov VY | title = Synaptically released zinc gates long-term potentiation in fear conditioning pathways | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 41 | pages = 15218–23 | date = October 2006 | pmid = 17005717 | pmc = 1622803 | doi = 10.1073/pnas.0607131103 | bibcode = 2006PNAS..10315218K | doi-access = free }}</ref> as well as some gaseous molecules such as [[nitric oxide]] (NO), [[carbon monoxide]] (CO), and [[hydrogen sulfide]] (H<sub>2</sub>S).<ref>{{cite web|url=http://www.marsdd.com/mars-library/international-symposium-on-nitric-oxide-dr-john-andrews/|title=International Symposium on Nitric Oxide – Dr. John Andrews – MaRS|work=MaRS|url-status=dead|archive-url=https://web.archive.org/web/20141014083429/http://www.marsdd.com/mars-library/international-symposium-on-nitric-oxide-dr-john-andrews/|archive-date=14 October 2014}}</ref> The gases are produced in the neural cytoplasm and are immediately diffused through the cell membrane into the extracellular fluid and into nearby cells to stimulate production of second messengers. Soluble gas neurotransmitters are difficult to study, as they act rapidly and are immediately broken down, existing for only a few seconds.{{cn|date=January 2025}}

The most prevalent transmitter is [[glutamate]], which is excitatory at well over 90% of the synapses in the human brain.<ref name=twsNovK11/> The next most prevalent is gamma-Aminobutyric Acid, or GABA, which is inhibitory at more than 90% of the synapses that do not use glutamate. Although other transmitters are used in fewer synapses, they may be very important functionally: the great majority of psychoactive drugs exert their effects by altering the actions of some neurotransmitter systems, often acting through transmitters other than glutamate or GABA. Addictive drugs such as cocaine and amphetamines exert their effects primarily on the dopamine system. The addictive [[opiate]] drugs exert their effects primarily as functional analogs of [[opioid peptides]], which, in turn, regulate dopamine levels.{{cn|date=January 2025}}

===List of neurotransmitters, peptides, and gaseous signaling molecules===

{{incomplete list|date=January 2017}}
{| class="wikitable unsortable" style="width:100%"
|<!--Start of inner tables-->
{| class="sortable wikitable" style="width:100%"
|+ Neurotransmitters
 |-
! scope="col" style="width: 15%;" | '''Category'''
! scope="col" style="width: 24%;" | '''Name'''
! scope="col" style="width: 6%;" class="unsortable" | <small>'''Abbreviation'''</small>
! scope="col" style="width: 31%;" | '''[[Metabotropic]]'''
! scope="col" style="width: 24%;" | '''[[Ionotropic]]'''
 |-
|{{abbrlink| Small| Small molecule}}: [[Amino acid]]s ([[Arginine|Arg]]) || [[Arginine]] || Arg, R ||[[Alpha-2 adrenergic receptor|α<sub>2</sub>-Adrenergic receptor]]s, [[imidazoline receptor]]s || [[NMDA receptor]]s
 |-
| Small: Amino acids || [[Aspartate]] || Asp, D || – || [[NMDA receptor]]s
 |-
| Small: Amino acids || [[Glutamate]] || Glu, E ||[[Metabotropic glutamate receptor]]s || [[NMDA receptor]]s, [[kainate receptor]]s, [[AMPAR]]s
 |-
| Small: Amino acids || [[Gamma-aminobutyric acid]] || GABA || [[GABAB receptor|GABA<sub>B</sub> receptor]]s || [[GABAA receptor|GABA<sub>A</sub> receptor]]s, [[GABAA-rho receptor|GABA<sub>A</sub>-ρ receptor]]s
 |-
| Small: Amino acids || [[Glycine]] || Gly, G || – || [[NMDA receptor]]s, [[glycine receptor]]s
 |-
| Small: Amino acids || [[D-serine|<small>D</small>-serine]] || Ser, S || – || [[NMDA receptor]]s
 |-
| Small: Acetylcholine || [[Acetylcholine]] || ACh ||[[Muscarinic acetylcholine receptor]]s || [[Nicotinic acetylcholine receptor]]s
 |-
| Small: [[Monoamine neurotransmitter|Monoamine]] ([[Phenylalanine|Phe]]/[[Tyrosine|Tyr]]) || [[Dopamine]] || DA || [[Dopamine receptor]]s, [[trace amine-associated receptor&nbsp;1]]<ref name="DA IUPHAR">{{cite web|title=Dopamine: Biological activity | url=http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=biology&ligandId=940|work=IUPHAR/BPS guide to pharmacology|publisher=International Union of Basic and Clinical Pharmacology|access-date=29 January 2016}}</ref><ref name="Miller+Grandy 2016">{{cite journal | vauthors = Grandy DK, Miller GM, Li JX | title = "TAARgeting Addiction"--The Alamo Bears Witness to Another Revolution: An Overview of the Plenary Symposium of the 2015 Behavior, Biology and Chemistry Conference | journal = Drug and Alcohol Dependence | volume = 159 | pages = 9–16 | date = February 2016 | pmid = 26644139 | pmc = 4724540 | doi = 10.1016/j.drugalcdep.2015.11.014 | quote = TAAR1 is a high-affinity receptor for METH/AMPH and DA }}</ref> || –
 |-
| Small: Monoamine ([[Phenylalanine|Phe]]/[[Tyrosine|Tyr]]) || [[Norepinephrine]] (noradrenaline) || NE, NAd || [[Adrenergic receptor]]s || –
 |-
| Small: Monoamine ([[Phenylalanine|Phe]]/[[Tyrosine|Tyr]]) || [[Epinephrine]] (adrenaline) || Epi, Ad || [[Adrenergic receptor]]s || –
 |-
| Small: Monoamine ([[Tryptophan|Trp]]) || [[Serotonin]] (5-hydroxytryptamine) || 5-HT || [[Serotonin receptor]]s (all except 5-HT<sub>3</sub>) || [[5-HT3|5-HT<sub>3</sub>]]
 |-
| Small: Monoamine ([[Histidine|His]]) || [[Histamine]] || H || [[Histamine receptor]]s || –
 |-
| Small: [[Trace amine]] ([[Phenylalanine|Phe]]) || [[Phenethylamine]] || PEA || [[Trace amine-associated receptor]]s [[TAAR1]], [[TAAR2]] || –
 |-
| Small: Trace amine ([[Phenylalanine|Phe]]) || [[N-methylphenethylamine|''N''-methylphenethylamine]] || NMPEA || [[TAAR1]] || –
 |-
| Small: Trace amine ([[Phenylalanine|Phe]]/[[Tyrosine|Tyr]]) || [[Tyramine]] || TYR || [[TAAR1]], [[TAAR2]] || –
 |-
| Small: Trace amine ([[Phenylalanine|Phe]]/[[Tyrosine|Tyr]]) || [[octopamine]] || Oct || [[TAAR1]] || –
 |-
| Small: Trace amine ([[Phenylalanine|Phe]]/[[Tyrosine|Tyr]]) || [[Synephrine]] || Syn || [[TAAR1]] || –
 |-
| Small: Trace amine ([[Tryptophan|Trp]]) || [[Tryptamine]] ||  || [[TAAR1]], various [[serotonin receptor]]s || –
 |-
| Small: Trace amine ([[Tryptophan|Trp]]) || [[N-methyltryptamine|''N''-methyltryptamine]] || NMT || [[TAAR1]], various [[serotonin receptor]]s || –
 |-
| Lipid || [[Anandamide]] || AEA || [[Cannabinoid receptor]]s || –
 |-
| Lipid || [[2-Arachidonoylglycerol]] || 2-AG || [[Cannabinoid receptor]]s || –
 |-
| Lipid || [[2-Arachidonyl glyceryl ether]] || 2-AGE || [[Cannabinoid receptor]]s || –
 |-
| Lipid || [[N-Arachidonoyl dopamine|''N''-Arachidonoyl dopamine]] || NADA || [[Cannabinoid receptor]]s || [[TRPV1]]
 |-
| Lipid || [[Virodhamine]] ||   || [[Cannabinoid receptor]]s || –
 |-
| Small: [[Purine]] || [[Adenosine]] || Ado || [[Adenosine receptor]]s || –
 |-
| Small: Purine || [[Adenosine triphosphate]] || ATP || [[P2Y receptor]]s || [[P2X receptor]]s
 |-
| Small: Purine || [[Nicotinamide adenine dinucleotide]] || β-NAD || [[P2Y receptor]]s || [[P2X receptor]]s
 |-
|}
{| class="wikitable sortable" style="width:100%"
|+ [[Neuropeptide]]s
 |-
! scope="col" style="width: 15%;" | '''Category'''
! scope="col" style="width: 24%;" | '''Name'''
! scope="col" style="width: 6%;" class="unsortable" | <small>'''Abbreviation'''</small>
! scope="col" style="width: 31%;" | '''[[Metabotropic]]'''
! scope="col" style="width: 24%;" | '''[[Ionotropic]]'''
 |-
| [[Bombesin-like peptides]]|| [[Bombesin]] ||  || BBR1-2-3 || –
 |-
| Bombesin-like peptide|| [[Gastrin releasing peptide]] || GRP || – || –
 |-
| Bombesin-like peptide|| [[Neuromedin B]] || NMB || [[Neuromedin B receptor]] || –
 |-
| Bradykinins || [[Bradykinin]] ||   || [[Bradykinin receptor B1|B1]], [[Bradykinin receptor B2|B2]] || –
 |-
| [[Amylin family|Calcitonin/CGRP family]]|| [[Calcitonin]] ||   || [[Calcitonin receptor]] || –
 |-
| Amylin family|Calcitonin/CGRP family|| [[Calcitonin gene-related peptide]] || CGRP  || [[CALCRL]] || –
 |-
| [[Corticotropin-releasing factor family|Corticotropin-releasing factors]]|| [[Corticotropin-releasing hormone]] || CRH || [[Corticotropin-releasing hormone receptor 1|CRHR1]] || –
 |-
| Corticotropin-releasing factors|| [[Urocortin]] ||  || [[Corticotropin-releasing hormone receptor 1|CRHR1]] || –
 |-
| Galanins || [[Galanin]] ||  || [[GALR1]], [[GALR2]], [[GALR3]] || –
 |-
| Galanins || [[Galanin-like peptide]] ||  || [[GALR1]], [[GALR2]], [[GALR3]] || –
 |-
| Gastrins || [[Gastrin]] ||  || [[Cholecystokinin B receptor]] || –
 |-
| Gastrins || [[Cholecystokinin]] || CCK || [[Cholecystokinin receptor]]s || –
 |-
| [[Granin]]s || [[Chromogranin A]] || ChgA || – || –
 |-
| [[Melanocortin]]s || [[Adrenocorticotropic hormone]] || ACTH || [[ACTH receptor]] || –
 |-
| Melanocortins || [[Proopiomelanocortin]] || POMC || [[Melanocortin 4 receptor]] || –
 |-
| Melanocortins || [[Melanocyte-stimulating hormone]]s || MSH || [[Melanocortin receptor]]s || –
 |-
| [[Neurohypophyseal]]s || [[Vasopressin]]  || AVP || [[Vasopressin receptor]]s || –
 |-
| Neurohypophyseals || [[Oxytocin]] || OT || [[Oxytocin receptor]] || –
 |-
| Neurohypophyseals || [[Neurophysin I]] ||   || – || –
 |-
| Neurohypophyseals || [[Neurophysin II]] ||   || – || –
 |-
| Neurohypophyseals || [[Copeptin]] ||   || – || –
 |-
| Neuromedins || [[Neuromedin U]] || NmU  ||[[Neuromedin U receptor 1|NmUR1]], [[Neuromedin U receptor 2|NmUR2]]|| –
 |-
| Neuropeptide B/W || [[Neuropeptide B]] || NPB || [[NPBWR1|NPBW1]], [[Neuropeptides B/W receptor 2|NPBW2]] || –
 |-
| Neuropeptide B/W || [[Neuropeptide S]] || NPS || [[Neuropeptide S receptor]]s || –
 |-
| Neuropeptide Y || [[Neuropeptide Y]] || NY || [[Neuropeptide Y receptor]]s || –
 |-
| Neuropeptide Y || [[Pancreatic polypeptide]] || PP || – || –
 |-
| Neuropeptide Y || [[Peptide YY]] || PYY || – || –
 |-
| [[Opioid]]s || [[Enkephalins]] ||   || [[Delta opioid receptor|δ-Opioid receptor]] || –
 |-
| Opioids || [[Dynorphins]] ||   || [[Kappa opioid receptor|κ-Opioid receptor]] || –
 |-
| Opioids || [[Neoendorphins]] ||   || [[Kappa opioid receptor|κ-Opioid receptor]] || –
 |-
| Opioids || [[Endorphins]] ||   || [[Mu opioid receptor|μ-Opioid receptor]]s || –
 |-
| Opioids || [[Endomorphins]] ||   || [[Mu opioid receptor|μ-Opioid receptor]]s || –
 |-
| Opioids || [[Morphine#Human biosynthesis|Morphine]] ||   || [[Mu opioid receptor|μ-Opioid receptor]]s || –
 |-
| Opioids || [[Nociceptin|Nociceptin/orphanin FQ]] || N/OFQ || [[Nociceptin receptor]]s || –
 |-
| [[Orexin]]s || [[Orexin A]] || OX-A || [[Orexin receptor]]s || –
 |-
| Orexins || [[Orexin B]] || OX-B || [[Orexin receptor]]s || –
 |-
| [[Parathyroid hormone family]] || [[Parathyroid hormone-related protein]] || PTHrP || – || –
 |-
| [[RFamide peptide family|RFamides]] || [[Kisspeptin]] || KiSS || [[GPR54]] || –
 |-
| RFamides || [[Neuropeptide FF]] || NPFF || NPFF1, NPFF2 || –
 |-
| RFamides || [[Prolactin-releasing peptide]] || PrRP|| [[Prolactin-releasing peptide receptor|PrRPR]] || –
 |-
| RFamides || [[Pyroglutamylated RFamide peptide]] || QRFP || [[Pyroglutamylated RFamide peptide receptor|GPR103]] || –
 |-
| [[Secretin family|Secretins]] || [[Secretin]] ||   || [[Secretin receptor]] || –
 |-
| Secretins || [[Motilin]] ||   || [[Motilin receptor]] || –
 |-
| Secretins || [[Glucagon]] ||   || [[Glucagon receptor]] || –
 |-
| Secretins || [[Glucagon-like peptide-1]] || GLP-1 || [[Glucagon-like peptide 1 receptor]] || –
 |-
| Secretins || [[Glucagon-like peptide-2]] || GLP-2 || [[Glucagon-like peptide 2 receptor]] || –
 |-
| Secretins || [[Vasoactive intestinal peptide]] || VIP || [[Vasoactive intestinal peptide receptor]]s || –
 |-
| Secretins || [[Growth hormone–releasing hormone]] || GHRH || [[Growth-hormone-releasing hormone receptor|Growth hormone–releasing hormone receptor]] || –
 |-
| Secretins || [[Pituitary adenylate cyclase-activating peptide]] || PACAP || [[ADCYAP1R1]] || –
 |-
| Somatostatins || [[Somatostatin]] ||  || [[Somatostatin receptor]]s || –
 |-
| [[Tachykinin peptides|Tachykinins]] || [[Neurokinin A]] ||   || – || –
 |-
| Tachykinins || [[Neurokinin B]] ||   || – || –
 |-
| Tachykinins || [[Substance P]] ||   || – || –
 |-
| Tachykinins || [[Neuropeptide K]] ||   || – || –
 |-
| Other || [[Agouti-related peptide]] || AgRP || [[Melanocortin receptor]] –
 |-
| Other || [[N-Acetylaspartylglutamate|''N''-Acetylaspartylglutamate]] || NAAG || [[Metabotropic glutamate receptor 3]] (mGluR3) || –
 |-
| Other || [[Cocaine- and amphetamine-regulated transcript]] || CART || Unknown [[Gi alpha subunit|G<sub>i</sub>/G<sub>o</sub>]]-coupled receptor<ref name="pmid21855138">{{cite journal | vauthors = Lin Y, Hall RA, Kuhar MJ | title = CART peptide stimulation of G protein-mediated signaling in differentiated PC12 cells: identification of PACAP 6-38 as a CART receptor antagonist | journal = Neuropeptides | volume = 45 | issue = 5 | pages = 351–8 | date = October 2011 | pmid = 21855138 | pmc = 3170513 | doi = 10.1016/j.npep.2011.07.006 }}</ref> || –
 |-
| Other || [[Gonadotropin-releasing hormone]] || GnRH|| [[gonadotropin-releasing hormone receptor|GnRHR]] || –
|-
| Other || [[Thyrotropin-releasing hormone]] || TRH|| [[Thyrotropin-releasing hormone receptor|TRHR]] || –
 |-
| Other || [[Melanin-concentrating hormone]] || MCH|| [[Melanin-concentrating hormone receptor|MCHR]] 1,2 || –
 |-
|}
{| class="wikitable sortable" style="width:100%"
|+ [[Gasotransmitter]]s
! scope="col" style="width: 15%;" | '''Category'''
! scope="col" style="width: 24%;" | '''Name'''
! scope="col" style="width: 6%;" class="unsortable" | <small>'''Abbreviation'''</small>
! scope="col" style="width: 31%;" | '''[[Metabotropic]]'''
! scope="col" style="width: 24%;" | '''[[Ionotropic]]'''
 |-
|[[Gaseous signaling molecule]] || [[Nitric oxide]] || NO || Soluble [[guanylyl cyclase]] || –
 |-
|Gaseous signaling molecule|| [[Carbon monoxide]] || CO || – || [[Heme]] bound to [[potassium channel]]s
 |-
|Gaseous signaling molecule|| [[Hydrogen sulfide]] || H2S || – || –
 |-
|}
|- <!--End of inner tables-->
|}

==Neurotransmitter systems {{anchor|table}}==
Neurons expressing certain types of neurotransmitters sometimes form distinct systems, where activation of the system affects large volumes of the brain, called [[volume transmission]]. Major neurotransmitter systems include the [[noradrenaline]] (norepinephrine) system, the [[dopamine]] system, the [[serotonin]] system, and the [[cholinergic]] system, among others. [[Trace amine]]s have a modulatory effect on neurotransmission in [[monoamine]] pathways (i.e., dopamine, norepinephrine, and serotonin pathways) throughout the brain via signaling through [[TAAR1|trace amine-associated receptor&nbsp;1]].<ref name="Miller">{{cite journal | vauthors = Miller GM | title = The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity | journal = Journal of Neurochemistry | volume = 116 | issue = 2 | pages = 164–76 | date = January 2011 | pmid = 21073468 | pmc = 3005101 | doi = 10.1111/j.1471-4159.2010.07109.x }}</ref><ref name="E Weihe">{{cite journal | vauthors = Eiden LE, Weihe E | title = VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse | journal = Annals of the New York Academy of Sciences | volume = 1216 | issue = 1 | pages = 86–98 | date = January 2011 | pmid = 21272013 | pmc = 4183197 | doi = 10.1111/j.1749-6632.2010.05906.x | quote = VMAT2 is the CNS vesicular transporter for not only the biogenic amines DA, NE, EPI, 5-HT, and HIS, but likely also for the trace amines TYR, PEA, and thyronamine (THYR)&nbsp;... [Trace aminergic] neurons in mammalian CNS would be identifiable as neurons expressing VMAT2 for storage, and the biosynthetic enzyme aromatic amino acid decarboxylase (AADC). | bibcode = 2011NYASA1216...86E }}</ref> A brief comparison of these systems follows:
<!--"Neurotransmitter system" and other articles redirect to the anchor in the wikitable title-->
{| class="wikitable" style="width:92%"
|+Neurotransmitter systems in the brain
|-
! System !! Pathway origin and projections !! Regulated cognitive processes and behaviors
|-
!id=Noradrenaline|Noradrenaline system<br /><ref name="VTA inputs">{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071481274 | page = 155 | edition = 2nd | chapter = Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin | quote= Different subregions of the VTA receive glutamatergic inputs from the prefrontal cortex, orexinergic inputs from the lateral hypothalamus, cholinergic and also glutamatergic and GABAergic inputs from the laterodorsal tegmental nucleus and pedunculopontine nucleus, noradrenergic inputs from the locus ceruleus, serotonergic inputs from the raphe nuclei, and GABAergic inputs from the nucleus accumbens and ventral pallidum.}}</ref><ref name="Noradrenergic pathways">{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071481274 | pages = 145, 156–157 | edition = 2nd | chapter = Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin | quote=Descending NE fibers modulate afferent pain signals.&nbsp;... The locus ceruleus (LC), which is located on the floor of the fourth ventricle in the rostral pons, contains more than 50% of all noradrenergic neurons in the brain; it innervates both the forebrain (eg, it provides virtually all the NE to the cerebral cortex) and regions of the brainstem and spinal cord.&nbsp;... The other noradrenergic neurons in the brain occur in loose collections of cells in the brainstem, including the lateral tegmental regions.  These neurons project largely within the brainstem and spinal cord. NE, along with 5HT, ACh, histamine, and orexin, is a critical regulator of the sleep-wake cycle and of levels of arousal.&nbsp;... LC firing may also increase anxiety&nbsp;...Stimulation of β-adrenergic receptors in the amygdala results in enhanced memory for stimuli encoded under strong negative emotion&nbsp;... Epinephrine occurs in only a small number of central neurons, all located in the medulla. Epinephrine is involved in visceral functions, such as control of respiration.<!--Note: the noradrenergic pathways are based upon a projection diagram that can't be quoted.-->}}</ref><ref name=Rang>{{cite book | vauthors = Rang HP |title=Pharmacology |publisher=Churchill Livingstone |location=Edinburgh |year=2003 |pages= 474 for noradrenaline system, page 476 for dopamine system, page 480 for serotonin system and page 483 for cholinergic system |isbn=978-0-443-07145-4 }}</ref><ref name="ARAS" /><ref name="NHM - ascending reticular activating system" /><ref name=Rinaman>{{cite journal | vauthors = Rinaman L | title = Hindbrain noradrenergic A2 neurons: diverse roles in autonomic, endocrine, cognitive, and behavioral functions | journal = American Journal of Physiology. Regulatory, Integrative and Comparative Physiology | volume = 300 | issue = 2 | pages = R222-35 | date = February 2011 | pmid = 20962208 | pmc = 3043801 | doi = 10.1152/ajpregu.00556.2010 }}</ref>
| '''Noradrenergic pathways''':
* [[Locus coeruleus]] (LC) projections
:* LC → [[Amygdala]] and [[Hippocampus]]
:* LC → [[Brain stem]] and [[Spinal cord]]
:* LC → [[Cerebellum]]
:* LC → [[Cerebral cortex]]
:* LC → [[Hypothalamus]]
:* LC → [[Tectum]]
:* LC → [[Thalamus]]
:* LC → [[Ventral tegmental area]]
* [[Lateral tegmental field]] (LTF) projections
:* LTF → [[Brain stem]] and [[Spinal cord]]
:* LTF → [[Olfactory bulb]]
|
* anxiety
* [[arousal]] (wakefulness)
* [[circadian rhythm]]
* [[cognitive control]] and [[working memory]] (co-regulated by dopamine)
* feeding and [[energy homeostasis]]
* [[medullary respiratory center|medullary control of respiration]]
* negative emotional memory
* [[nociception]] (perception of pain)
* [[reward system|reward]] (minor role)
|-
!id=Dopamine|Dopamine system<br /><ref name=Rang /><ref name="ARAS" /><ref name="NHM - ascending reticular activating system" /><ref name="Malenka pathways">{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071481274 | pages = 147–148, 154–157 | edition = 2nd | chapter = Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin | quote=Neurons from the SNc densely innervate the dorsal striatum where they play a critical role in the learning and execution of motor programs.  Neurons from the VTA innervate the ventral striatum (nucleus accumbens), olfactory bulb, amygdala, hippocampus, orbital and medial prefrontal cortex, and cingulate cortex. VTA DA neurons play a critical role in motivation, reward-related behavior, attention, and multiple forms of memory.&nbsp;... Thus, acting in diverse terminal fields, dopamine confers motivational salience ("wanting") on the reward itself or associated cues (nucleus accumbens shell region), updates the value placed on different goals in light of this new experience (orbital prefrontal cortex), helps consolidate multiple forms of memory (amygdala and hippocampus), and encodes new motor programs that will facilitate obtaining this reward in the future (nucleus accumbens core region and dorsal striatum).&nbsp;... DA has multiple actions in the prefrontal cortex.  It promotes the "cognitive control" of behavior: the selection and successful monitoring of behavior to facilitate attainment of chosen goals.  Aspects of cognitive control in which DA plays a role include working memory, the ability to hold information "on line" in order to guide actions, suppression of prepotent behaviors that compete with goal-directed actions, and control of attention and thus the ability to overcome distractions.&nbsp;... Noradrenergic projections from the LC thus interact with dopaminergic projections from the VTA to regulate cognitive control.&nbsp;...}}</ref><ref name="Reward and aversion MSNs">{{cite journal | vauthors = Calipari ES, Bagot RC, Purushothaman I, Davidson TJ, Yorgason JT, Peña CJ, Walker DM, Pirpinias ST, Guise KG, Ramakrishnan C, Deisseroth K, Nestler EJ | display-authors = 6 | title = In vivo imaging identifies temporal signature of D1 and D2 medium spiny neurons in cocaine reward | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 113 | issue = 10 | pages = 2726–31 | date = March 2016 | pmid = 26831103 | pmc = 4791010 | doi = 10.1073/pnas.1521238113 | quote = Previous work has demonstrated that optogenetically stimulating D1 MSNs promotes reward, whereas stimulating D2 MSNs produces aversion. | doi-access = free | bibcode = 2016PNAS..113.2726C }}</ref><ref name="Dopaminergic pathways and reward system review">{{cite journal | vauthors = Ikemoto S | title = Brain reward circuitry beyond the mesolimbic dopamine system: a neurobiological theory | journal = Neuroscience and Biobehavioral Reviews | volume = 35 | issue = 2 | pages = 129–50 | date = November 2010 | pmid = 20149820 | pmc = 2894302 | doi = 10.1016/j.neubiorev.2010.02.001 | quote = Recent studies on intracranial self-administration of neurochemicals (drugs) found that rats learn to self-administer various drugs into the mesolimbic dopamine structures–the posterior ventral tegmental area, medial shell nucleus accumbens and medial olfactory tubercle.&nbsp;... In the 1970s it was recognized that the olfactory tubercle contains a striatal component, which is filled with GABAergic medium spiny neurons receiving glutamatergic inputs form cortical regions and dopaminergic inputs from the VTA and projecting to the ventral pallidum just like the nucleus accumbens }}<br />[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2894302/figure/F3/ Figure 3: The ventral striatum and self-administration of amphetamine]</ref>
| '''[[Dopaminergic pathways]]''':
* [[Ventral tegmental area]] (VTA) projections
:* VTA → [[Amygdala]]
:* VTA → [[Cingulate cortex]]
:* VTA → [[Hippocampus]]
:* VTA → [[Ventral striatum]] ([[Mesolimbic pathway]])
:* VTA → [[Olfactory bulb]]
:* VTA → [[Prefrontal cortex]] ([[Mesocortical pathway]])
* [[Nigrostriatal pathway]]
:* [[Substantia nigra pars compacta]] → [[Dorsal striatum]]
* [[Tuberoinfundibular pathway]]
:* [[Arcuate nucleus]] → [[Median eminence]]
* Hypothalamospinal projection
:* [[Hypothalamus]] → [[Spinal cord]]
* [[Incertohypothalamic pathway]]
:* [[Zona incerta]] → Hypothalamus
|
* [[arousal]] (wakefulness)
* aversion
* [[cognitive control]] and [[working memory]] (co-regulated by norepinephrine)
* emotion and [[mood (psychology)|mood]]
* motivation ([[motivational salience]])
* [[motor system|motor function]] and control
* [[positive reinforcement]]
* [[reward system|reward]] (primary mediator)
* [[sexual arousal]], [[orgasm]], and [[sexual refractory period|refractory period]] (via neuroendocrine regulation)
|-
!id=Histamine|Histamine system<br /><ref name="ARAS">{{cite journal | vauthors = Iwańczuk W, Guźniczak P | title = Neurophysiological foundations of sleep, arousal, awareness and consciousness phenomena. Part 1 | journal = Anaesthesiology Intensive Therapy | volume = 47 | issue = 2 | pages = 162–7 | date = 2015 | pmid = 25940332 | doi = 10.5603/AIT.2015.0015 | quote = The ascending reticular activating system (ARAS) is responsible for a sustained wakefulness state.&nbsp;... The thalamic projection is dominated by cholinergic neurons originating from the pedunculopontine tegmental nucleus of pons and midbrain (PPT) and laterodorsal tegmental nucleus of pons and midbrain (LDT) nuclei [17, 18]. The hypothalamic projection involves noradrenergic neurons of the locus coeruleus (LC) and serotoninergic neurons of the dorsal and median raphe nuclei (DR), which pass through the lateral hypothalamus and reach axons of the histaminergic tubero-mamillary nucleus (TMN), together forming a pathway extending into the forebrain, cortex and hippocampus. Cortical arousal also takes advantage of dopaminergic neurons of the substantia nigra (SN), ventral tegmenti area (VTA) and the periaqueductal grey area (PAG). Fewer cholinergic neurons of the pons and midbrain send projections to the forebrain along the ventral pathway, bypassing the thalamus [19, 20]. | doi-access = free }}</ref><ref name="NHM - ascending reticular activating system">{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York, USA | isbn = 9780071481274 | page = 295 | edition = 2nd | chapter = Chapter 12: Sleep and Arousal | quote = The ARAS is a complex structure consisting of several different circuits including the four monoaminergic pathways&nbsp;... The norepinephrine pathway originates from the locus ceruleus (LC) and related brainstem nuclei; the serotonergic neurons originate from the raphe nuclei within the brainstem as well; the dopaminergic neurons originate in ventral tegmental area (VTA); and the histaminergic pathway originates from neurons in the tuberomammillary nucleus (TMN) of the posterior hypothalamus. As discussed in Chapter 6, these neurons project widely throughout the brain from restricted collections of cell bodies. Norepinephrine, serotonin, dopamine, and histamine have complex modulatory functions and, in general, promote wakefulness. The PT in the brain stem is also an important component of the ARAS. Activity of PT cholinergic neurons (REM-on cells) promotes REM sleep. During waking, REM-on cells are inhibited by a subset of ARAS norepinephrine and serotonin neurons called REM-off cells.}}</ref><ref name="Histamine pathways">{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071481274 | pages = 175–176 | edition = 2nd | chapter = Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin | quote = Within the brain, histamine is synthesized exclusively by neurons with their cell bodies in the tuberomammillary nucleus (TMN) that lies within the posterior hypothalamus. There are approximately 64000 histaminergic neurons per side in humans. These cells project throughout the brain and spinal cord. Areas that receive especially dense projections include the cerebral cortex, hippocampus, neostriatum, nucleus accumbens, amygdala, and hypothalamus. &nbsp;... While the best characterized function of the histamine system in the brain is regulation of sleep and arousal, histamine is also involved in learning and memory&nbsp;...It also appears that histamine is involved in the regulation of feeding and energy balance.}}</ref>
|'''Histaminergic pathways''':
* [[Tuberomammillary nucleus]] (TMN) projections
:* TMN → [[Cerebral cortex]]
:* TMN → [[Hippocampus]]
:* TMN → [[Neostriatum]]
:* TMN → [[Nucleus accumbens]]
:* TMN → [[Amygdala]]
:* TMN → [[Hypothalamus]]
|
* [[arousal]] (wakefulness)
* feeding and [[energy homeostasis]]
* learning
* memory
|-
!id=Serotonin|Serotonin system<br /><ref name="VTA inputs" /><ref name=Rang /><ref name="ARAS" /><ref name="NHM - ascending reticular activating system" /><ref name="Serotonergic pathways">{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071481274 | pages = 158–160 | edition = 2nd | chapter = Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin | quote= [The] dorsal raphe preferentially innervates the cerebral cortex, thalamus, striatal regions (caudate-putamen and nucleus accumbens), and dopaminergic nuclei of the midbrain (eg, the substantia nigra and ventral tegmental area), while the median raphe innervates the hippocampus, septum, and other structures of the limbic forebrain.&nbsp;... it is clear that 5HT influences sleep, arousal, attention, processing of sensory information in the cerebral cortex, and important aspects of emotion (likely including aggression) and mood regulation.&nbsp;...The rostral nuclei, which include the nucleus linearis, dorsal raphe, medial raphe, and raphe pontis, innervate most of the brain, including the cerebellum.  The caudal nuclei, which comprise the raphe magnus, raphe pallidus, and raphe obscuris, have more limited projections that terminate in the cerebellum, brainstem, and spinal cord.}}</ref><ref>{{cite web| vauthors = Nestler EJ |title= Brain Reward Pathways |url= http://neuroscience.mssm.edu/nestler/brainRewardpathways.html|website=Icahn School of Medicine at Mount Sinai|publisher=Nestler Lab|access-date=16 August 2014|quote=The dorsal raphe is the primary site of serotonergic neurons in the brain, which, like noradrenergic neurons, pervasively modulate brain function to regulate the state of activation and mood of the organism.}}</ref><ref name="pmid21216242">{{cite journal | vauthors = Marston OJ, Garfield AS, Heisler LK | title = Role of central serotonin and melanocortin systems in the control of energy balance | journal = European Journal of Pharmacology | volume = 660 | issue = 1 | pages = 70–9 | date = June 2011 | pmid = 21216242 | doi = 10.1016/j.ejphar.2010.12.024 }}</ref>
|'''[[Serotonergic pathways]]''':
[[Caudal nuclei]] (CN):<br />
[[Raphe magnus]], [[raphe pallidus]], and [[raphe obscurus]]
* Caudal projections
:* CN → [[Cerebral cortex]]
:* CN → [[Thalamus]]
:* CN → [[Caudate nucleus|Caudate]]-[[putamen]] and [[nucleus accumbens]]
:* CN → [[Substantia nigra]] and [[ventral tegmental area]]
:* CN → [[Cerebellum]]
:* CN → [[Spinal cord]]
[[Rostral nuclei]] (RN):<br />
[[Nucleus linearis]], [[dorsal raphe]], [[medial raphe]], and [[raphe pontis]]
* Rostral projections
:* RN → [[Amygdala]]
:* RN → [[Cingulate cortex]]
:* RN → [[Hippocampus]]
:* RN → [[Hypothalamus]]
:* RN → [[Neocortex]]
:* RN → [[Septum]]
:* RN → [[Thalamus]]
:* RN → [[Ventral tegmental area]]
|
* [[arousal]] (wakefulness)
* [[body temperature]] regulation
* emotion and [[mood (psychology)|mood]], potentially including aggression
* feeding and [[energy homeostasis]]
* [[reward system|reward]] (minor role)
* sensory perception
|-
!id=Acetylcholine|Acetylcholine system<br /><ref name="VTA inputs" /><ref name=Rang /><ref name="ARAS" /><ref name="NHM - ascending reticular activating system" /><ref name="Cholinergic pathways">{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071481274 | pages = 167–175 | edition = 2nd | chapter = Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin | quote= The basal forebrain cholinergic nuclei are comprised the medial septal nucleus (Ch1), the vertical nucleus of the diagonal band (Ch2), the horizontal limb of the diagonal band (Ch3), and the nucleus basalis of Meynert (Ch4).  Brainstem cholinergic nuclei include the pedunculopontine nucleus (Ch5), the laterodorsal tegmental nucleus (Ch6), the medial habenula (Ch7), and the parabigeminal nucleus (Ch8).}}</ref>
|'''Cholinergic pathways''':
Forebrain cholinergic nuclei (FCN):<br />
[[Nucleus basalis of Meynert]], [[medial septal nucleus]], and [[nucleus of diagonal band|diagonal band]]
* Forebrain nuclei projections
:*FCN → [[Hippocampus]]
:*FCN → [[Cerebral cortex]]
:*FCN → [[Limbic cortex]] and [[sensory cortex]]
Striatal tonically active cholinergic neurons (TAN)
:*TAN → [[Medium spiny neuron]]

Brainstem cholinergic nuclei (BCN):<br />
[[Pedunculopontine nucleus]], [[laterodorsal tegmental nucleus|laterodorsal tegmentum]], [[medial habenula]], and<br />[[parabigeminal nucleus]]
* Brainstem nuclei projections
:*BCN → [[Ventral tegmental area]]
:*BCN → [[Thalamus]]

|
* [[arousal]] (wakefulness)
* emotion and [[mood (psychology)|mood]]
* learning
* [[motor system|motor function]]
* motivation ([[motivational salience]])
* [[Memory#Short-term|short-term memory]]
* [[reward system|reward]] (minor role)
|-
!id=Adrenaline|Adrenaline system<br /><ref>{{cite journal | vauthors = Guyenet PG, Stornetta RL, Bochorishvili G, Depuy SD, Burke PG, Abbott SB | title = C1 neurons: the body's EMTs | journal = American Journal of Physiology. Regulatory, Integrative and Comparative Physiology | volume = 305 | issue = 3 | pages = R187-204 | date = August 2013 | pmid = 23697799 | doi = 10.1152/ajpregu.00054.2013 | pmc = 3743001 }}</ref><ref>{{cite journal | vauthors = Stornetta RL, Guyenet PG | title = C1 neurons: a nodal point for stress? | journal = Experimental Physiology | volume = 103 | issue = 3 | pages = 332–336 | date = March 2018 | pmid = 29080216 | doi = 10.1113/EP086435 | pmc = 5832554 }}</ref>
| '''Adrenergic pathways''':
* [[Rostral ventrolateral medulla]] (RVLM) projections
:* RVLM → [[Spinal cord]]
:* RVLM → [[Brain stem]]
:* RVLM → [[Hypothalamus]]
|
* [[medullary respiratory center|medullary control of respiration]]
* [[sympathetic nervous system]]
* feeding and [[energy homeostasis]]
* [[arousal]]
* [[Stress (biology)|stress]]
|}

{{further|Neural pathway|Neuromodulation|List of regions in the human brain}}

==Drug effects==
Understanding the effects of drugs on neurotransmitters comprises a significant portion of research initiatives in the field of [[neuroscience]]. Most neuroscientists involved in this field of research believe that such efforts may further advance our understanding of the circuits responsible for various neurological diseases and disorders, as well as ways to effectively treat and someday possibly prevent or cure such illnesses.<ref name="Brainfacts revised">{{cite web|title=Neuron Conversations: How Brain Cells Communicate|url=http://www.brainfacts.org/brain-basics/cell-communication/articles/2012/neuron-conversations/|website=Brainfacts.org|access-date=2 December 2014}}</ref>{{medical citation needed|date=December 2017}}

Drugs can influence behavior by altering neurotransmitter activity. For instance, drugs can decrease the rate of synthesis of neurotransmitters by affecting the synthetic enzyme(s) for that neurotransmitter. When neurotransmitter syntheses are blocked, the amount of neurotransmitters available for release becomes substantially lower, resulting in a decrease in neurotransmitter activity. Some drugs block or stimulate the release of specific neurotransmitters.  Alternatively, drugs can prevent neurotransmitter storage in synaptic vesicles by causing the synaptic vesicle membranes to leak. Drugs that prevent a neurotransmitter from binding to its receptor are called [[receptor antagonist]]s. For example, drugs used to treat patients with schizophrenia such as haloperidol, chlorpromazine, and clozapine are antagonists at receptors in the brain for dopamine. Other drugs act by binding to a receptor and mimicking the normal neurotransmitter. Such drugs are called receptor [[agonist]]s. An example of a receptor agonist is [[morphine]], an opiate that mimics effects of the endogenous neurotransmitter [[β-endorphin]] to relieve pain. Other drugs interfere with the deactivation of a neurotransmitter after it has been released, thereby prolonging the action of a neurotransmitter. This can be accomplished by blocking re-uptake or inhibiting degradative enzymes. Lastly, drugs can also prevent an action potential from occurring, blocking neuronal activity throughout the central and peripheral [[nervous system]]. Drugs such as [[tetrodotoxin]] that block neural activity are typically lethal.{{cn|date=January 2025}}

Drugs targeting the neurotransmitter of major systems affect the whole system, which can explain the complexity of action of some drugs. [[Cocaine]], for example, blocks the re-uptake of [[dopamine]] back into the [[presynaptic]] neuron, leaving the neurotransmitter molecules in the [[synapse|synaptic gap]] for an extended period of time. Since the dopamine remains in the synapse longer, the neurotransmitter continues to bind to the receptors on the [[postsynaptic]] neuron, eliciting a pleasurable emotional response. Physical addiction to cocaine may result from prolonged exposure to excess dopamine in the synapses, which leads to the [[downregulation]] of some post-synaptic receptors. After the effects of the drug wear off, an individual can become depressed due to decreased probability of the neurotransmitter binding to a receptor. [[Fluoxetine]] is a [[selective serotonin re-uptake inhibitor]] (SSRI), which blocks re-uptake of serotonin by the presynaptic cell which increases the amount of serotonin present at the synapse and furthermore allows it to remain there longer, providing potential for the effect of naturally released serotonin.<ref name="InhibitingSerotoninSynthesis">{{cite journal | vauthors = Yadav VK, Ryu JH, Suda N, Tanaka KF, Gingrich JA, Schütz G, Glorieux FH, Chiang CY, Zajac JD, Insogna KL, Mann JJ, Hen R, Ducy P, Karsenty G | display-authors = 6 | title = Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum | journal = Cell | volume = 135 | issue = 5 | pages = 825–37 | date = November 2008 | pmid = 19041748 | pmc = 2614332 | doi = 10.1016/j.cell.2008.09.059 }}</ref> [[AMPT]] prevents the conversion of tyrosine to [[L-DOPA]], the precursor to dopamine; [[reserpine]] prevents dopamine storage within [[Synaptic vesicle|vesicles]]; and [[deprenyl]] inhibits [[monoamine oxidase]] (MAO)-B and thus increases dopamine levels.{{cn|date=January 2025}}

{| class="wikitable sortable"
|+ Drug–neurotransmitter interactions<ref>Carlson, N. R., & Birkett, M. A. (2017). Physiology of Behavior (12th ed.). Pearson, pp.&nbsp;100–115. {{ISBN|978-0134080918}}</ref>
!Drug
!Interacts with
!Receptor interaction
!Type
!Effects
|-
|[[Botulinum toxin]] (Botox)
|[[Acetylcholine]]
| –
|Antagonist
|Blocks [[acetylcholine]] release in PNS
Prevents muscle contractions
|-
|Black widow spider venom
|[[Acetylcholine]]
| –
|Agonist
|Promotes acetylcholine release in PNS
Stimulates muscle contractions
|-
|Neostigmine
|[[Acetylcholine]]
| –
| –
|Interferes with acetylcholinerase activity
Increases effects of ACh at receptors

Used to treat myasthenia gravis
|-
|[[Nicotine]]
|[[Acetylcholine]]
|[[Nicotinic acetylcholine receptor|Nicotinic]] (skeletal muscle)
|Agonist
|Increases ACh activity
Increases attention

Reinforcing effects
|-
|d-tubocurarine
|[[Acetylcholine]]
|[[Nicotinic acetylcholine receptor|Nicotinic]] (skeletal muscle)
|Antagonist
|Decreases activity at receptor site
|-
|[[Curare]]
|[[Acetylcholine]]
|[[Nicotinic acetylcholine receptor|Nicotinic]] (skeletal muscle)
|Antagonist
|Decreases ACh activity
Prevents muscle contractions
|-
|[[Muscarine]]
|[[Acetylcholine]]
|[[Muscarinic acetylcholine receptor|Muscarinic]] (heart and smooth muscle)
|Agonist
|Increases ACh activity
Toxic
|-
|[[Atropine]]
|[[Acetylcholine]]
|[[Muscarinic acetylcholine receptor|Muscarinic]] (heart and smooth muscle)
|Antagonist
|Blocks pupil constriction
Blocks saliva production
|-
|Scopolamine ([[hyoscine]])
|[[Acetylcholine]]
|[[Muscarinic acetylcholine receptor|Muscarinic]] (heart and smooth muscle)
|Antagonist
|Treats motion sickness and postoperative nausea and vomiting
|-
|AMPT
|Dopamine/norepinephrine
| –
| –
|Inactivates tyrosine hydroxylase and inhibits dopamine production
|-
|[[Reserpine]]
|Dopamine
| –
| –
|Prevents storage of dopamine and other monoamines in synaptic vesicles
Causes sedation and depression
|-
|[[Apomorphine]]
|Dopamine
|[[Dopamine receptor D2|D2 receptor]] (presynaptic autoreceptors/postsynaptic receptors)
|Antagonist (low dose) / direct agonist (high dose)
|Low dose: blocks autoreceptors
High dose: stimulates postsynaptic receptors
|-
|[[Amphetamine]]
|Dopamine/norepinephrine
| –
|Indirect agonist
|Releases dopamine, noradrenaline, and serotonin
Blocks reuptake<ref name="Miller" /><ref name="E Weihe" />
|-
|[[Methamphetamine]]
|Dopamine/norepinephrine
| –
| –
|Releases dopamine and noradrenaline

Blocks reuptake
|-
|[[Methylphenidate]]
|Dopamine
| –
| –
|Blocks reuptake
Enhances attention and impulse control in ADHD
|-
|[[Cocaine]]
|Dopamine
| –
|Indirect agonist
|Blocks reuptake into presynapse
Blocks voltage-dependent sodium channels

Can be used as a topical anesthetic (eye drops)
|-
|Deprenyl
|Dopamine
| –
|Agonist
|Inhibits MAO-B
Prevents destruction of dopamine
|-
|[[Chlorpromazine]]
|Dopamine
|[[Dopamine receptor D2|D2 Receptors]]
|Antagonist
|Blocks D2 receptors
Alleviates hallucinations
|-
|[[MPTP]]
|Dopamine
| –
| –
|Results in Parkinson-like symptoms
|-
|PCPA
|Serotonin (5-HT)
| –
|Antagonist
|Disrupts serotonin synthesis by blocking the activity of [[tryptophan hydroxylase]]
|-
|[[Ondansetron]]
|Serotonin (5-HT)
|[[5-HT receptor|5-HT<sub>3</sub> receptors]]
|Antagonist
|Reduces side effects of chemotherapy and radiation
Reduces nausea and vomiting
|-
|[[Buspirone]]
|Serotonin (5-HT)
|[[5-HT1A receptor|5-HT<sub>1A</sub> receptors]]
|Partial agonist
|Treats symptoms of anxiety and depression
|-
|[[Fluoxetine]]
|Serotonin (5-HT)
| supports [[Serotonin|5-HT]] reuptake
|SSRI
|Inhibits reuptake of serotonin
Treats depression, some anxiety disorders, and OCD<ref name="InhibitingSerotoninSynthesis" /> Common examples: [[Prozac]] and [[Sarafem]]
|-
|[[Fenfluramine]]
|Serotonin (5-HT)
| –
| –
|Causes release of serotonin
Inhibits reuptake of serotonin

Used as an appetite suppressant
|-
|[[Lysergic acid diethylamide]]
|Serotonin (5-HT)
|Post-synaptic 5-HT<sub>2A</sub> receptors
|Direct agonist
|Produces visual perception distortions
Stimulates 5-HT<sub>2A</sub> receptors in forebrain
|-
|Methylenedioxy&shy;methamphetamine ([[MDMA]])
|Serotonin (5-HT)/norepinphrine
| –
| –
|Stimulates release of serotonin and norepinephrine and inhibits the reuptake
Causes excitatory and hallucinogenic effects
|-
|[[Strychnine]]
|Glycine
| –
|Antagonist
|Causes severe muscle spasms<ref>{{Cite web |url=http://emergency.cdc.gov/agent/strychnine/basics/facts.asp |title=CDC Strychnine. Facts about Strychnine |website=Public Health Emergency Preparedness & Response |access-date=7 May 2018}}</ref>
|-
|[[Diphenhydramine]]
|Histamine
|
|
|Crosses blood–brain barrier to cause drowsiness
|-
|[[Tetrahydrocannabinol]] (THC)
|Endocannabinoids
|Cannabinoid (CB) receptors
|Agonist
|Produces analgesia and sedation
Increases appetite

Cognitive effects
|-
|Rimonabant
|Endocannabinoids
|Cannabinoid (CB) receptors
|Antagonist
|Suppresses appetite
Used in smoking cessation
|-
|MAFP
|Endocannabinoids
| –
| –
|Inhibits FAAH
Used in research to increase cannabinoid system activity
|-
|AM1172
|Endocannabinoids
| –
| –
|Blocks cannabinoid reuptake
Used in research to increase cannabinoid system activity
|-
|Anandamide (endogenous)
| –
|Cannabinoid (CB) receptors; 5-HT<sub>3</sub> receptors
| –
|Reduce nausea and vomiting
|-
|[[Caffeine]]
|Adenosine
|Adenosine receptors
|Antagonist
|Blocks adenosine receptors
Increases wakefulness
|-
|[[PCP (drug)|PCP]]
|Glutamate
|[[NMDA receptor]]
|Indirect antagonist
|Blocks PCP binding site
Prevents calcium ions from entering neurons

Impairs learning
|-
|[[AP5]]
|Glutamate
|[[NMDA receptor]]
|Antagonist
|Blocks glutamate binding site on NMDA receptor

Impairs synaptic plasticity and certain forms of learning
|-
|[[Ketamine]]
|Glutamate
|[[NMDA receptor]]
|Antagonist
|Used as anesthesia
Induces trance-like state, helps with pain relief and sedation
|-
|[[N-Methyl-D-aspartic acid|NMDA]]
|Glutamate
|[[NMDA receptor]]
|Agonist
|Used in research to study NMDA receptor
Ionotropic receptor
|-
|[[AMPA]]
|Glutamate
|[[AMPA receptor]]
|Agonist
|Used in research to study AMPA receptor
Ionotropic receptor
|-
|Allyglycine
|GABA
| –
| –
|Inhibits GABA synthesis
Causes seizures
|-
|[[Muscimol]]
|GABA
|[[GABA receptor]]
|Agonist
|Causes sedation
|-
|[[Bicuculline|Bicuculine]]
|GABA
|GABA receptor
|Antagonist
|Causes Seizures
|-
|[[Benzodiazepine]]s
|GABA
|[[GABAA receptor|GABA<sub>A</sub> receptor]]
|Indirect agonists
|Anxiolytic, sedation, memory impairment, muscle relaxation
|-
|[[Barbiturate]]s
|GABA
|[[GABAA receptor|GABA<sub>A</sub> receptor]]
|Indirect agonists
|Sedation, memory impairment, muscle relaxation
|-
|[[Alcohol (drug)|Alcohol]]
|GABA
|[[GABA receptor]]
|Indirect agonist
|Sedation, memory impairment, muscle relaxation
|-
|[[Picrotoxin]]
|GABA
|[[GABAA receptor|GABA<sub>A</sub> receptor]]
|Indirect antagonist
|High doses cause seizures
|-
|[[Tiagabine]]
|GABA
| –
|Antagonist
|GABA transporter antagonist
Increase availability of GABA

Reduces the likelihood of seizures
|-
|[[Moclobemide]]
|Norepinephrine
| –
|Agonist
|Blocks MAO-A to treat depression
|-
|[[Idazoxan]]
|Norepinephrine
|alpha-2 adrenergic autoreceptors
|Agonist
|Blocks alpha-2 autoreceptors
Used to study norepinephrine system
|-
|Fusaric acid
|Norepinephrine
| –
| –
|Inhibits activity of dopamine beta-hydroxylase which blocks the production of norepinephrine
Used to study norepinephrine system without affecting dopamine system
|-
|Opiates ([[opium]], [[morphine]], [[heroin]], and [[oxycodone]])
|Opioids
|Opioid receptor<ref name="Fallows" />
|Agonists
|Analgesia, sedation, and reinforcing effects
|-
|[[Naloxone]]
|Opioids
| –
|Antagonist
|Reverses opiate intoxication or overdose symptoms (i.e. problems with breathing)
|}

===Agonists===
{{Main|Agonist}}
{{expand section|coverage of full agonists and their distinction from partial agonist and inverse agonist.|date=August 2015}}
An agonist is a chemical capable of binding to a receptor, such as a neurotransmitter receptor, and initiating the same reaction typically produced by the binding of the endogenous substance.<ref>{{cite web|url=http://www.merriam-webster.com/dictionary/agonist |title=Agonist – Definition and More from the Free Merriam-Webster Dictionary |publisher=Merriam-webster.com |access-date=25 August 2014}}</ref> An agonist of a neurotransmitter will thus initiate the same receptor response as the transmitter. In neurons, an agonist drug may activate neurotransmitter receptors either directly or indirectly. Direct-binding agonists can be further characterized as [[Agonist#Types of agonists|full agonist]]s, [[partial agonist]]s, [[inverse agonist]]s.<ref>Atack J., Lavreysen H. (2010) Agonist. In: Stolerman I.P. (eds) Encyclopedia of Psychopharmacology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-68706-1_1565</ref><ref>{{cite journal|author1-link=Bryan Roth| vauthors = Roth BL | title = DREADDs for Neuroscientists | journal = Neuron | volume = 89 | issue = 4 | pages = 683–694 | date = February 2016 | pmid = 26889809 | pmc = 4759656 | doi = 10.1016/j.neuron.2016.01.040 | doi-access = free }}</ref>

[[Direct agonist]]s act similar to a neurotransmitter by binding directly to its associated receptor site(s), which may be located on the presynaptic neuron or postsynaptic neuron, or both.<ref name="Direct and indirect agonists" /> Typically, neurotransmitter receptors are located on the postsynaptic neuron, while neurotransmitter [[autoreceptor]]s are located on the presynaptic neuron, as is the case for [[monoamine neurotransmitter]]s;<ref name="Miller" /> in some cases, a neurotransmitter utilizes [[retrograde neurotransmission]], a type of feedback signaling in neurons where the neurotransmitter is released postsynaptically and binds to target receptors located on the presynaptic neuron.<ref name="Cannabinoid-Orexin systemic cross-talk" />{{#tag:ref|In the central nervous system, [[anandamide]] other [[endocannabinoid]]s utilize retrograde neurotransmission, since their release is postsynaptic, while their target receptor, [[cannabinoid receptor 1]] (CB1), is presynaptic.<ref name="Cannabinoid-Orexin systemic cross-talk">{{cite journal | vauthors = Flores A, Maldonado R, Berrendero F | title = Cannabinoid-hypocretin cross-talk in the central nervous system: what we know so far | journal = Frontiers in Neuroscience | volume = 7 | pages = 256 | date = December 2013 | pmid = 24391536 | pmc = 3868890 | doi = 10.3389/fnins.2013.00256 | doi-access = free }}<br />{{bull}}[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868890/figure/F1/ Figure 1: Schematic of brain CB1 expression and orexinergic neurons expressing OX1 or OX2]<br />{{bull}}[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868890/figure/F2/ Figure 2: Synaptic signaling mechanisms in cannabinoid and orexin systems]</ref> The [[cannabis]] plant contains [[Tetrahydrocannabinol|Δ<sup>9</sup>-tetrahydrocannabinol]], which is a direct agonist at CB1.<ref name="Cannabinoid-Orexin systemic cross-talk" />|group="note"|name="retrograde"}} [[Nicotine]], a compound found in [[tobacco]], is a direct agonist of most [[nicotinic acetylcholine receptor]]s, mainly located in [[cholinergic neuron]]s.<ref name=Fallows>{{cite web|url=http://ocw.mit.edu/ans7870/SP/SP.236/S09/lecturenotes/drugchart.htm |title=Neurotransmitters and Drugs Chart |publisher=Ocw.mit.edu |access-date=25 August 2014}}</ref> [[Opiate]]s, such as [[morphine]], [[heroin]], [[hydrocodone]], [[oxycodone]], [[codeine]], and [[methadone]], are [[mu opioid receptor|μ-opioid receptor]] agonists; this action mediates their [[euphoria]]nt and [[analgesia|pain relieving]] properties.<ref name=Fallows/>

[[Indirect agonist]]s increase the binding of neurotransmitters at their target receptors by stimulating the release or preventing the [[reuptake]] of neurotransmitters.<ref name="Direct and indirect agonists">{{cite book| vauthors = Ries RK, Fiellin DA, Miller SC |title=Principles of addiction medicine.|date=2009|publisher=Wolters Kluwer/Lippincott Williams & Wilkins|location=Philadelphia|isbn=9780781774772|pages=709–710|edition=4th|url=https://books.google.com/books?id=j6GGBud8DXcC&pg=PA709|access-date=16 August 2015}}</ref> Some indirect agonists [[releasing agent|trigger neurotransmitter release]] and [[reuptake inhibitor|prevent neurotransmitter reuptake]]. [[Amphetamine]], for example, is an indirect agonist of postsynaptic dopamine, norepinephrine, and serotonin receptors in each their respective neurons;<ref name="Miller" /><ref name="E Weihe" /> it produces both neurotransmitter release into the presynaptic neuron and subsequently the synaptic cleft and prevents their reuptake from the synaptic cleft by activating [[TAAR1]], a presynaptic [[G protein-coupled receptor]], and binding to a site on [[VMAT2]], a type of [[monoamine transporter]] located on [[synaptic vesicles]] within [[monoamine neurotransmitter|monoamine neurons]].<ref name="Miller" /><ref name="E Weihe" />

=== Antagonists ===
{{Main|Receptor antagonist}}
An antagonist is a chemical that acts within the body to reduce the physiological activity of another chemical substance (such as an opiate); especially one that opposes the action on the nervous system of a drug or a substance occurring naturally in the body by combining with and blocking its nervous receptor.<ref name="M-W revised">{{cite web|title=Antagonist|url=http://www.merriam-webster.com/medical/antagonist|website=Medical definition of Antagonist|access-date=5 November 2014}}</ref>

There are two main types of antagonist: direct-acting Antagonist and indirect-acting Antagonists:
# Direct-acting antagonist- which takes up space present on receptors which are otherwise taken up by neurotransmitters themselves. This results in neurotransmitters being blocked from binding to the receptors. An example of one of the most common is called Atropine.
# Indirect-acting antagonist- drugs that inhibit the release/production of neurotransmitters (e.g., [[Reserpine]]).

==== Drug antagonists ====
An antagonist drug is one that attaches (or binds) to a site called a receptor without activating that receptor to produce a biological response. It is therefore said to have no intrinsic activity. An antagonist may also be called a receptor "blocker" because they block the effect of an agonist at the site. The pharmacological effects of an antagonist, therefore, result in preventing the corresponding receptor site's agonists (e.g., drugs, hormones, neurotransmitters) from binding to and activating it. Antagonists may be "competitive" or "irreversible".{{cn|date=March 2025}}

A competitive antagonist competes with an agonist for binding to the receptor. As the concentration of antagonist increases, the binding of the agonist is progressively inhibited, resulting in a decrease in the physiological response. High concentration of an antagonist can completely inhibit the response. This inhibition can be reversed, however, by an increase of the concentration of the agonist, since the agonist and antagonist compete for binding to the receptor. Competitive antagonists, therefore, can be characterized as shifting the [[dose–response relationship]] for the agonist to the right. In the presence of a competitive antagonist, it takes an increased concentration of the agonist to produce the same response observed in the absence of the antagonist.{{cn|date=March 2025}}

An irreversible antagonist binds so strongly to the receptor as to render the receptor unavailable for binding to the agonist. Irreversible antagonists may even form covalent chemical bonds with the receptor. In either case, if the concentration of the irreversible antagonist is high enough, the number of unbound receptors remaining for agonist binding may be so low that even high concentrations of the agonist do not produce the maximum biological response.<ref name="Encyclopedia.com 2">{{cite web | vauthors = Goeders NE |title=Antagonist |url=http://www.encyclopedia.com/topic/Antagonist.aspx |access-date=2 December 2014 |location=Encyclopedia of Drugs, Alcohol, and Addictive Behavior |year=2001}}</ref>

===Precursors===
{{Phenylalanine biosynthesis|align=right}}
While intake of neurotransmitter [[Precursor (chemistry)|precursors]] does increase neurotransmitter synthesis, evidence is mixed as to whether [[neurotransmitter release]] and postsynaptic receptor firing is increased. Even with increased neurotransmitter release, it is unclear whether this will result in a long-term increase in neurotransmitter signal strength, since the nervous system can adapt to changes such as increased neurotransmitter synthesis and may therefore maintain constant firing.<ref name="NeurotransmitterPrecursorsDepression">{{cite journal | vauthors = Meyers S | title = Use of neurotransmitter precursors for treatment of depression | journal = Alternative Medicine Review | volume = 5 | issue = 1 | pages = 64–71 | date = February 2000 | pmid = 10696120 | url = http://www.thorne.com/altmedrev/.fulltext/5/1/64.pdf | url-status = dead | df = dmy-all | archive-url = https://web.archive.org/web/20040805114256/http://www.thorne.com/altmedrev/.fulltext/5/1/64.pdf | archive-date = 5 August 2004 }}</ref>{{ums|date=December 2017}} Some neurotransmitters may have a role in depression and there is some evidence to suggest that intake of precursors of these neurotransmitters may be useful in the treatment of mild and moderate depression.<ref name="NeurotransmitterPrecursorsDepression"/>{{ums|date=December 2017}}<ref name="ManagementDepressionSerotoninPrecursors">{{cite journal | vauthors = van Praag HM | title = Management of depression with serotonin precursors | journal = Biological Psychiatry | volume = 16 | issue = 3 | pages = 291–310 | date = March 1981 | pmid = 6164407 }}</ref>

====Catecholamine and trace amine precursors====
[[L-DOPA|<small>L</small>-DOPA]], a precursor of [[dopamine]] that crosses the [[blood–brain barrier]], is used in the treatment of [[Parkinson's disease]]. For depressed patients where low activity of the neurotransmitter [[norepinephrine]] is implicated, there is only little evidence for benefit of neurotransmitter precursor administration. [[L-phenylalanine]] and [[L-tyrosine]] are both precursors for [[dopamine]], [[norepinephrine]], and [[epinephrine]]. These conversions require [[vitamin B6]], [[vitamin C]], and [[S-adenosylmethionine]]. A few studies suggest potential antidepressant effects of L-phenylalanine and L-tyrosine, but there is much room for further research in this area.<ref name="NeurotransmitterPrecursorsDepression"/>{{ums|date=December 2017}}

====Serotonin precursors====

Administration of [[L-tryptophan]], a precursor for [[serotonin]], is seen to double the production of serotonin in the brain. It is significantly more effective than a placebo in the treatment of mild and moderate depression.<ref name="NeurotransmitterPrecursorsDepression"/>{{ums|date=December 2017}} This conversion requires [[vitamin C]].<ref name=serotonin /> [[5-hydroxytryptophan]] (5-HTP), also a precursor for [[serotonin]], is more effective than a placebo.<ref name="NeurotransmitterPrecursorsDepression"/>{{ums|date=December 2017}}

== Diseases and disorders<!-- This section needs a lot more detail! --> ==
The following sections describe how imbalances or dysfunction in specific neurotransmitters—dopamine, serotonin, and glutamate—have been tentatively linked to various mental or neurological disorders.

=== Dopamine ===

For example, problems in producing dopamine (mainly in the [[substantia nigra]]) can result in [[Parkinson's disease]], a disorder that affects a person's ability to move as they want to, resulting in stiffness, tremors or shaking, and other symptoms. Some studies suggest that having too little or too much dopamine or problems using dopamine in the thinking and feeling regions of the brain may play a role in disorders like [[schizophrenia]] or [[attention deficit hyperactivity disorder]] (ADHD). Dopamine is also involved in addiction and drug use, as most recreational drugs cause an influx of dopamine in the brain (especially [[opioid]] and [[methamphetamine]]s) that produces a pleasurable feeling, which is why users constantly crave drugs.<ref>{{Cite web |title=Dopamine: What It Is, Function & Symptoms |url=https://my.clevelandclinic.org/health/articles/22581-dopamine |archive-url=http://web.archive.org/web/20250303012437/https://my.clevelandclinic.org/health/articles/22581-dopamine |archive-date=2025-03-03 |access-date=2025-03-07 |website=Cleveland Clinic |language=en}}</ref>

=== Serotonin ===

Similarly, after some research suggested that drugs that block the recycling, or reuptake, of serotonin seemed to help some people diagnosed with depression, it was theorized that people with [[Major depressive disorder|depression]] might have lower-than-normal serotonin levels. Though widely popularized, this theory was not borne out in subsequent research.<ref>{{cite journal | vauthors = Healy D | title = Serotonin and depression | journal = BMJ | volume = 350 | pages = h1771 | date = April 2015 | pmid = 25900074 | doi = 10.1136/bmj.h1771 | s2cid = 38726584 }}</ref> Therefore, [[Selective serotonin reuptake inhibitor|selective serotonin reuptake inhibitors (SSRIs)]] are used to increase the amounts of serotonin in synapses.{{cn|date=March 2025}}

=== Glutamate ===

[[File:CAPON Binds Nitric Oxide Synthase, Regulating NMDA Receptor–Mediated Glutamate Neurotransmission.png|thumb|CAPON binds nitric oxide synthase, regulating NMDA receptor–mediated glutamate neurotransmission]]
Furthermore, problems with producing or using glutamate have been suggestively and tentatively linked to many mental disorders, including [[autism]], [[obsessive–compulsive disorder]] (OCD), [[schizophrenia]], and [[major depressive disorder|depression]].<ref name="NIH Brain Basics">{{cite web |title=NIMH Brain Basics |url=http://www.nimh.nih.gov/health/educational-resources/brain-basics/brain-basics.shtml |publisher=[[U.S. National Institutes of Health]] |access-date=29 October 2014 |archive-date=29 October 2014 |archive-url=https://web.archive.org/web/20141029234833/http://www.nimh.nih.gov/health/educational-resources/brain-basics/brain-basics.shtml |url-status=dead }}</ref> Having too much glutamate has been linked to neurological diseases such as [[Parkinson's disease]], [[multiple sclerosis]], [[Alzheimer's disease]], [[stroke]], and [[Amyotrophic lateral sclerosis|ALS]] (amyotrophic lateral sclerosis).<ref>{{cite journal | vauthors = Bittigau P, Ikonomidou C | title = Glutamate in neurologic diseases | journal = Journal of Child Neurology | volume = 12 | issue = 8 | pages = 471–85 | date = November 1997 | pmid = 9430311 | doi = 10.1177/088307389701200802 | s2cid = 1258390 }}</ref>

==Neurotransmitter imbalance==
Generally, there are no scientifically established "norms" for appropriate levels or "balances" of different neurotransmitters. In most cases, it is practically impossible to measure neurotransmitter levels in the brain or body at any given moment. Neurotransmitters regulate each other's release, and weak consistent imbalances in this mutual regulation were linked to temperament in healthy people.<ref>Netter, P. (1991) Biochemical variables in the study of temperament. In Strelau, J. & Angleitner, A. (Eds.), Explorations in temperament: International perspectives on theory and measurement 147–161. New York: Plenum Press.</ref><ref>{{cite journal | vauthors = Trofimova I, Robbins TW | title = Temperament and arousal systems: A new synthesis of differential psychology and functional neurochemistry | journal = Neuroscience and Biobehavioral Reviews | volume = 64 | pages = 382–402 | date = May 2016 | pmid = 26969100 | doi = 10.1016/j.neubiorev.2016.03.008 | hdl = 11375/26202 | s2cid = 13937324 | url = https://www.repository.cam.ac.uk/handle/1810/274784 | hdl-access = free }}</ref><ref>Cloninger CR, Svrakic DM, Przybeck TR. A psychobiological model of temperament and character" ''Arch Gen Psychiatry'' 1993; 50:975-990.</ref><ref>{{cite book |year=2016| vauthors = Trofimova IN | chapter = The interlocking between functional aspects of activities and a neurochemical model of adult temperament. | veditors = Arnold MC | title = Temperaments: Individual Differences, Social and Environmental Influences and Impact on Quality of Life. | location = New York | publisher = Nova Science Publishers, Inc. |pages=77–147}}</ref><ref>{{cite journal | vauthors = Depue RA, Morrone-Strupinsky JV | title = A neurobehavioral model of affiliative bonding: implications for conceptualizing a human trait of affiliation | journal = The Behavioral and Brain Sciences | volume = 28 | issue = 3 | pages = 313–50; discussion 350–95 | date = June 2005 | pmid = 16209725 | doi = 10.1017/s0140525x05000063 | doi-broken-date = 22 May 2025 }}</ref> However, significant imbalances or disruptions in neurotransmitter systems are associated with various diseases and mental disorders, including Parkinson's disease, depression, insomnia, Attention Deficit Hyperactivity Disorder (ADHD), anxiety, memory loss, dramatic weight changes, and addictions. Some of these conditions are also related to neurotransmitter switching, a phenomenon where neurons change the type of neurotransmitters they release.<ref>{{Cite journal |last=Spitzer |first=Nicholas C. |date=2017-07-25 |title=Neurotransmitter Switching in the Developing and Adult Brain |url=https://www.annualreviews.org/doi/10.1146/annurev-neuro-072116-031204 |journal=Annual Review of Neuroscience |language=en |volume=40 |issue=1 |pages=1–19 |doi=10.1146/annurev-neuro-072116-031204 |pmid=28301776 |issn=0147-006X}}</ref><ref>{{Cite web |last=Dolan |first=Eric W. |date=2024-11-13 |title=Neurotransmitter switching in early development predicts autism-related behaviors |url=https://www.psypost.org/neurotransmitter-switching-in-early-development-predicts-autism-related-behaviors/ |access-date=2024-11-22 |website=PsyPost - Psychology News |language=en-US}}</ref><ref>{{Cite journal |last1=Pratelli |first1=Marta |last2=Hakimi |first2=Anna M. |last3=Thaker |first3=Arth |last4=Jang |first4=Hyeonseok |last5=Li |first5=Hui-quan |last6=Godavarthi |first6=Swetha K. |last7=Lim |first7=Byung Kook |last8=Spitzer |first8=Nicholas C. |date=2024-09-26 |title=Drug-induced change in transmitter identity is a shared mechanism generating cognitive deficits |journal=Nature Communications |language=en |volume=15 |issue=1 |pages=8260 |doi=10.1038/s41467-024-52451-x |pmid=39327428 |issn=2041-1723|pmc=11427679 |bibcode=2024NatCo..15.8260P }}</ref> Chronic physical or emotional stress can be a contributor to neurotransmitter system changes. Genetics also plays a role in neurotransmitter activities.

Apart from recreational use, medications that directly and indirectly interact with one or more transmitter or its receptor are commonly prescribed for psychiatric and psychological issues. Notably, drugs interacting with [[serotonin]] and [[norepinephrine]] are prescribed to patients with problems such as depression and anxiety—though the notion that there is much solid medical evidence to support such interventions has been widely criticized.<ref>Leo, J., & Lacasse, J. (10 October 2007). The Media and the Chemical Imbalance Theory of Depression. Retrieved 1 December 2014, from http://psychrights.org/articles/TheMediaandChemicalImbalanceTheoryofDepression.pdf</ref> Studies shown that dopamine imbalance has an influence on multiple sclerosis and other neurological disorders.<ref name="Dopamine Imbalance">{{cite journal | vauthors = Dobryakova E, Genova HM, DeLuca J, Wylie GR | title = The dopamine imbalance hypothesis of fatigue in multiple sclerosis and other neurological disorders | journal = Frontiers in Neurology | volume = 6 | pages = 52 | date = 12 March 2015 | pmid = 25814977 | pmc = 4357260 | doi = 10.3389/fneur.2015.00052 | doi-access = free }}</ref>

== See also ==
{{Portal|Medicine}}
{{div col|colwidth=20em}}
* {{slink|BK channel#Cellular level}}
* [[Kiss-and-run fusion]]
* [[Natural neuroactive substance]]
* [[Neuroendocrine]]
* [[Neuroendocrinology]]
* [[Neuropsychopharmacology]]
* [[Neurotransmission]]
* [[Neurotransmitter analog]]
* [[Neurotransmitter release]]
* [[Neural pathway]]
* [[Neuromodulation]]
* [[False neurotransmitter]]
{{div col end}}

==Notes==
{{Reflist|group="note"}}
{{reflist|group=nb}}

== References ==
{{Reflist|30em}}

== External links ==
{{Commons}}
{{Wikibooks|Neuroscience/Cellular Neurobiology/Neurotransmitters}}
* {{Cite book |last1=Purves |first1=Dale |url=https://www.ncbi.nlm.nih.gov/books/NBK10957/ |title=What Defines a Neurotransmitter? |last2=Augustine |first2=George J. |last3=Fitzpatrick |first3=David |last4=Katz |first4=Lawrence C. |last5=LaMantia |first5=Anthony-Samuel |last6=McNamara |first6=James O. |last7=Williams |first7=S. Mark |date=2001 |journal=Neuroscience |publisher=Sinauer Associates |isbn=0-87893-742-0 |edition=2nd |location=Sunderland (MA) |language=en |chapter=Chapter 6. Neurotransmitters}}
* {{Cite book |last1=Holz |first1=Ronald W. |url=https://www.ncbi.nlm.nih.gov/books/NBK27911/ |title=Synaptic Transmission |last2=Fisher |first2=Stephen K. |date=1999 |journal=Basic Neurochemistry: Molecular, Cellular and Medical Aspects |publisher=Lippincott-Raven |isbn=0-397-51820-X |editor-last=Siegel |editor-first=George J |edition=6th |location=Philadelphia |language=en |chapter=Chapter 10. Synaptic Transmission and Cellular Signaling: An Overview |editor-last2=Agranoff |editor-first2=Bernard W |editor-last3=Albers |editor-first3=R Wayne |editor-last4=Fisher |editor-first4=Stephen K |editor-last5=Uhler |editor-first5=Michael D}}
* [http://faculty.washington.edu/chudler/chnt1.html Neurotransmitters and Neuroactive Peptides at Neuroscience for Kids website]

{{Neuroscience}}
{{Neurotransmitters}}
{{Cell signaling}}
{{Neurotransmitter systems}}

{{Authority control}}

[[Category:Neurotransmitters| ]]
[[Category:Molecular neuroscience]]
[[Category:Neuroscience]]