Editing Neurotransmitter (section)

==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}}