Editing 5-Hydroxytryptophan

{{Distinguish|5-hydroxytryptamine}}
{{About|5-hydroxytryptophan as a biological compound|its role as a medication and supplement|Oxitriptan}}
{{Use dmy dates|date=September 2015}}
{{Chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 477224677
| ImageFile = 5-Hydroxy-L-Tryptophan (5-HTP).svg
| ImageClass = skin-invert
| ImageAlt = Skeletal formula
| ImageFile1 = 5-Hydroxy-L-tryptophan-3D-balls.png
| ImageAlt1 = Ball-and-stick model
| IUPACName = 2-amino-3-(5-hydroxy-1''H''-indol-3-yl)propanoic acid
| OtherNames = 5-HTP; Oxitriptan; α-Carboxy-5-hydroxytryptamine; α-Carboxy-5-HT
|Section1={{Chembox Identifiers
| IUPHAR_ligand = 4671
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = C1LJO185Q9
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D07339
| InChI = 1/C11H12N2O3/c12-9(11(15)16)3-6-5-13-10-2-1-7(14)4-8(6)10/h1-2,4-5,9,13-14H,3,12H2,(H,15,16)/t9-/m0/s1
| InChIKey = LDCYZAJDBXYCGN-VIFPVBQEBZ
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 350221
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C11H12N2O3/c12-9(11(15)16)3-6-5-13-10-2-1-7(14)4-8(6)10/h1-2,4-5,9,13-14H,3,12H2,(H,15,16)/t9-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = LDCYZAJDBXYCGN-VIFPVBQESA-N
| CASNo_Ref = {{cascite|changed|CAS}}
| CASNo = 56-69-9 
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 388413
| PubChem = 144
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 17780
| SMILES = O=C(O)[C@@H](N)Cc2c1cc(O)ccc1[nH]c2
| MeSHName = 5-Hydroxytryptophan
  }}
|Section2={{Chembox Properties
| C=11 | H=12 | N=2 | O=3
| Appearance=
| Density=1.484 g/mL
| MeltingPtC = 298 to 300
| BoilingPtC=520.6
| Solubility=
  }}
|Section7={{Chembox Hazards
| MainHazards=
| FlashPtC=
| AutoignitionPtC =
  }}
}}

'''5-Hydroxytryptophan''' ('''5-HTP'''), used medically as '''oxitriptan''', is a [[natural product|naturally occurring]] [[amino acid]] and [[chemical compound|chemical]] [[precursor (chemistry)|precursor]] as well as a [[metabolic intermediate]] in the [[biosynthesis]] of the [[neurotransmitter]] [[serotonin]].

5-HTP can be manufactured and used as a [[drug]] and supplement with the {{Abbrlink|INN|International Nonproprietary Name}} ''[[oxitriptan]]''. Brand names include Cincofarm, Levothym, Levotonine, Oxyfan, Telesol, Tript-OH, and Triptum. As a drug, it is used in the treatment of [[depression (mood)|depression]] and for certain other indications.

==Production==
5-HTP is produced from the amino acid [[tryptophan]] through the action of the enzyme [[tryptophan hydroxylase]]. Tryptophan hydroxylase is one of the [[biopterin-dependent aromatic amino acid hydroxylases]]. Production of 5-HTP is the rate-limiting step in 5-HT (serotonin)  synthesis. 5-HTP is normally rapidly converted to 5-HT by amino acid decarboxylase.<ref name="TurnerLoftisBlackwell2006">{{cite journal | vauthors = Turner EH, Loftis JM, Blackwell AD | title = Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan | journal = Pharmacology & Therapeutics | volume = 109 | issue = 3 | pages = 325–338 | date = March 2006 | pmid = 16023217 | doi = 10.1016/j.pharmthera.2005.06.004 | s2cid = 2563606 | url = https://escholarship.org/uc/item/58h866d5 | quote = 5-HTP is commonly given to rats or mice to test the SSRI potency of putative antidepressants (O’Neil & Moore, 2003). This simple in vivo test measures the potency of a compound in potentiating the serotonin syndrome induced by the administration of 5-HTP (Grahame-Smith, 1971). The behavioral and physiological features of this syndrome include hypolocomotion, head twitch, forepaw treading, tremors, hindlimb abduction, flat body posture or hunched back, cyanosis, and hyperthermia. In rodents, 5-HTP induces a serotonin syndrome at dosages of 100– 200 mg/ kg (Casal et al., 2000; Nisijima et al., 2000, 2001; see Section 4.4.3 for more on serotonin syndrome).}}</ref>

==Metabolism==
5-HTP is [[decarboxylation|decarboxylated]] to [[serotonin]] (5-hydroxytryptamine or 5-HT) by the [[enzyme]] [[aromatic-L-amino-acid decarboxylase]] with the help of [[vitamin B6|vitamin B<sub>6</sub>]].<ref>{{cite journal | vauthors = Rahman MK, Nagatsu T, Sakurai T, Hori S, Abe M, Matsuda M | title = Effect of pyridoxal phosphate deficiency on aromatic L-amino acid decarboxylase activity with L-DOPA and L-5-hydroxytryptophan as substrates in rats | journal = Japanese Journal of Pharmacology | volume = 32 | issue = 5 | pages = 803–11 | date = October 1982 | pmid = 6983619 | doi = 10.1254/jjp.32.803 | doi-access = free }}</ref> This reaction occurs both in nervous tissue and in the liver.<ref>{{cite journal | vauthors = Bouchard S, Bousquet C, Roberge AG | title = Characteristics of dihydroxyphenylalanine/5-hydroxytryptophan decarboxylase activity in brain and liver of cat | journal = Journal of Neurochemistry | volume = 37 | issue = 3 | pages = 781–7 | date = September 1981 | pmid = 6974228 | doi = 10.1111/j.1471-4159.1982.tb12555.x | s2cid = 43853143 }}</ref> 5-HTP crosses the [[blood–brain barrier]],<ref>{{cite journal | vauthors = Nakatani Y, Sato-Suzuki I, Tsujino N, Nakasato A, Seki Y, Fumoto M, Arita H | title = Augmented brain 5-HT crosses the blood-brain barrier through the 5-HT transporter in rat | journal = The European Journal of Neuroscience | volume = 27 | issue = 9 | pages = 2466–72 | date = May 2008 | pmid = 18445233 | doi = 10.1111/j.1460-9568.2008.06201.x | s2cid = 18940166 }}</ref> while 5-HT does not. Excess 5-HTP, especially when administered with vitamin B<sub>6</sub>, is thought to be metabolized and excreted.<ref>{{cite journal | vauthors = Bouchard S, Roberge AG | title = Biochemical properties and kinetic parameters of dihydroxyphenylalanine--5-hydroxytryptophan decarboxylase in brain, liver, and adrenals of cat | journal = Canadian Journal of Biochemistry | volume = 57 | issue = 7 | pages = 1014–8 | date = July 1979 | pmid = 39668 | doi = 10.1139/o79-126 }}</ref><ref>{{cite journal | vauthors = Amamoto T, Sarai K | title = On the tryptophan-serotonin metabolism in manic-depressive disorders. Changes in plasma 5-HT and 5-HIAA levels and urinary 5-HIAA excretion following oral loading of L-5HTP in patients with depression | journal = Hiroshima Journal of Medical Sciences | volume = 25 | issue = 2–3 | pages = 135–40 | date = September 1976 | pmid = 1088369 }}</ref>

[[Image:trp-5ht-pathway.svg|class=skin-invert-image|center|600px|Metabolic pathway from tryptophan to serotonin.]]

{{Enzymatic Reaction
| forward_enzyme=[[Aromatic L-amino acid decarboxylase|AAAD]]
| reverse_enzyme=
| substrate=5-HTP
| product=[[Serotonin]]
| reaction_direction_(forward/reversible/reverse)=forward
| minor_forward_substrate(s)=[[Pyridoxal phosphate|PLP]]
| minor_forward_product(s)  =
| minor_reverse_substrate(s)=
| minor_reverse_product(s)  =
| substrate_image=5-Hydroxy-L-Tryptophan_(5-HTP).svg
| substrate_image_size=160px
| product_image=Serotonin (5-HT).svg
| product_image_size=125px
}}

==Dietary sources==
{{See also|Tryptophan#Dietary sources}}

Though 5-HTP is found in food only in insignificant quantities, it is a chemical involved intermediately in the metabolism of tryptophan, an amino acid found in all unfractionated foods, with lower total amino acid content correlating with increased tryptophan absorption.<ref>{{cite web|url=http://www.umm.edu/altmed/articles/5-hydroxytryptophan-000283.htm|title=5-Hydroxytryptophan|access-date=21 January 2010|publisher=University of Maryland Medical Center| archive-url= https://web.archive.org/web/20100106132618/http://www.umm.edu/altmed/articles/5-hydroxytryptophan-000283.htm| archive-date= 6 January 2010 | url-status=dead}}</ref>

==Use as a medication and supplement==
{{Main|Oxitriptan}}

5-HTP is used medically and as a supplement under the name ''[[oxitriptan]]'' in the treatment of [[depression (mood)|depression]] and for certain other indications.

It can be potentiated in [[combination drug|combination]] with a [[peripherally selective drug|peripherally selective]] [[aromatic L-amino acid decarboxylase|aromatic <small>L</small>-amino acid decarboxylase]] (AAAD) [[aromatic L-amino acid decarboxylase inhibitor|inhibitor]] such as [[carbidopa]] or [[benserazide]]. These agents increase the strength and duration of oxitriptan. An investigational combination formulation is [[oxitriptan/carbidopa]].

==Research==
===Psychedelic effects===
{{See also|Tryptophan#Psychedelic effects}}

5-HTP robustly produces the [[head-twitch response]] (HTR) in rodents when administered at relatively high doses.<ref name="KozlenkovGonzález-Maeso2013" /><ref name="SchmidBohn2018" /><ref name="JasterdelaFuenteRevengaGonzález-Maeso2022">{{cite journal | vauthors = Jaster AM, de la Fuente Revenga M, González-Maeso J | title = Molecular targets of psychedelic-induced plasticity | journal = J Neurochem | volume = 162 | issue = 1 | pages = 80–88 | date = July 2022 | pmid = 34741320 | pmc = 9068831 | doi = 10.1111/jnc.15536 | url = }}</ref><ref name="SchmidBohn2010">{{cite journal | vauthors = Schmid CL, Bohn LM | title = Serotonin, but not N-methyltryptamines, activates the serotonin 2A receptor via a β-arrestin2/Src/Akt signaling complex in vivo | journal = J Neurosci | volume = 30 | issue = 40 | pages = 13513–24 | date = October 2010 | pmid = 20926677 | pmc = 3001293 | doi = 10.1523/JNEUROSCI.1665-10.2010 | url = }}</ref><ref name="ShaharBotvinnikEsh-Zuntz2022">{{cite journal | vauthors = Shahar O, Botvinnik A, Esh-Zuntz N, Brownstien M, Wolf R, Lotan A, Wolf G, Lerer B, Lifschytz T | title = Role of 5-HT2A, 5-HT2C, 5-HT1A and TAAR1 Receptors in the Head Twitch Response Induced by 5-Hydroxytryptophan and Psilocybin: Translational Implications | journal = Int J Mol Sci | volume = 23 | issue = 22 | date = November 2022 | page = 14148 | pmid = 36430623 | pmc = 9698447 | doi = 10.3390/ijms232214148 | doi-access = free | url = | quote = HTR was first described in mice after administration of the serotonin precursor, 5-hydroxytryptophan (5-HTP) [22], and has been further characterized by subsequent investigators [23–29]. Although extensive research has documented the effect of 5-HTP to induce HTR in rodents [30–33], psychedelic effects have not been reported at doses administered to humans [34]. [...] 5-HTP-induced HTR has previously described by multiple authors [30–33,48]. However, 5-HTP has not been reported to have psychedelic effects in humans [49]. Although, overdoses of compounds that increase serotonin release can result in serotonin syndrome, which may include hallucinations [50,51], classic psychedelic effects resembling those induced by tryptaminergic and other psychedelic drugs have not been reported. In our study, administration of 5-HTP at 150–250 mg/kg induced significant HTR. The implications of administering equivalent high doses of 5-HTP to humans are unknown. There are two instances of administering up to 3000 mg 5-HTP per os per day but not as a single dose. Such prolonged exposure that can result in tolerance effects [49].}}</ref> It [[dose-dependently]] induces the HTR in mice across a dose range of 50 to 250{{nbsp}}mg/kg via [[intraperitoneal administration]], with an [[inverted U-shaped curve|inverted U-shaped]] [[dose–response curve]] and maximal induction of the HTR at a dose of 200{{nbsp}}mg/kg.<ref name="ShaharBotvinnikEsh-Zuntz2022" /><ref name="TurnerLoftisBlackwell2006" /> Similarly to the case of 5-HTP, [[intracerebroventricular injection]] of serotonin, but not peripheral administration of serotonin, produces the HTR.<ref name="SchmidBohn2018" /><ref name="KozlenkovGonzález-Maeso2013" /><ref name="SchmidBohn2010" /> The HTR is induced by [[serotonergic psychedelic]]s like [[lysergic acid diethylamide]] (LSD) and [[psilocybin]] and is a behavioral proxy of psychedelic effects.<ref name="CanalMorgan2012">{{cite journal | vauthors = Canal CE, Morgan D | title = Head-twitch response in rodents induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine: a comprehensive history, a re-evaluation of mechanisms, and its utility as a model | journal = Drug Test Anal | volume = 4 | issue = 7–8 | pages = 556–576 | date = 2012 | pmid = 22517680 | pmc = 3722587 | doi = 10.1002/dta.1333 | url = }}</ref><ref name="KozlenkovGonzález-Maeso2013" />

The HTR of 5-HTP is blocked by serotonin [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]] [[receptor antagonist|antagonist]]s, which block the [[hallucinogen]]ic effects of serotonergic psychedelics in humans, is prevented by [[aromatic L-amino acid decarboxylase|aromatic <small>L</small>-amino acid decarboxylase]] (AAAD) [[aromatic L-amino acid decarboxylase inhibitor|inhibitor]]s, which block conversion of 5-HTP into serotonin, and is potentiated by [[monoamine oxidase A]] (MAO-A) [[monoamine oxidase inhibitor|inhibitor]]s, which prevent the [[catabolism|degradation]] of serotonin and other [[endogenous]] [[substituted tryptamine|tryptamine]]s.<ref name="SchmidBohn2018">{{cite book | last1=Schmid | first1=Cullen L. | last2=Bohn | first2=Laura M. | title=5-HT2A Receptors in the Central Nervous System | chapter=βArrestins: Ligand-Directed Regulators of 5-HT2A Receptor Trafficking and Signaling Events | publisher=Springer International Publishing | publication-place=Cham | date=2018 | isbn=978-3-319-70472-2 | doi=10.1007/978-3-319-70474-6_2 | pages=31–55}}</ref><ref name="KozlenkovGonzález-Maeso2013" /><ref name="JasterdelaFuenteRevengaGonzález-Maeso2022" /><ref name="SchmidBohn2010" /><ref name="ShaharBotvinnikEsh-Zuntz2022" /> It is also suppressed by the serotonin [[5-HT1A receptor|5-HT<sub>1A</sub> receptor]] [[full agonist]] [[8-OH-DPAT]], is greatly augmented by the serotonin [[5-HT2C receptor|5-HT<sub>2C</sub> receptor]] antagonist [[RS-102221]], and is reduced by the [[trace amine-associated receptor 1]] (TAAR1) antagonist [[EPPTB]].<ref name="ShaharBotvinnikEsh-Zuntz2022" /> In addition, the HTR of 5-HTP is abolished by [[indolethylamine N-methyltransferase|indolethylamine ''N''-methyltransferase]] (INMT) [[enzyme inhibitor|inhibitor]]s, which block conversion of serotonin and other endogenous tryptamines into ''N''-[[methyl group|methylated]] tryptamines, such as [[N-Methylserotonin|''N''-methylserotonin]] (NMS; norbufotenin), [[bufotenin]] (5-hydroxy-''N'',''N''-dimethyltryptamine; 5-HO-DMT), and [[dimethyltryptamine|''N'',''N''-dimethyltryptamine]] (DMT).<ref name="KozlenkovGonzález-Maeso2013">{{cite book | last1=Kozlenkov | first1=Alexey | last2=González-Maeso | first2=Javier | title=The Neuroscience of Hallucinations | chapter=Animal Models and Hallucinogenic Drugs | publisher=Springer New York | publication-place=New York, NY | date=2013 | isbn=978-1-4614-4120-5 | doi=10.1007/978-1-4614-4121-2_14 | pages=253–277}}</ref><ref name="HalberstadtGeyer2018">{{cite book | vauthors = Halberstadt AL, Geyer MA | title = Behavioral Neurobiology of Psychedelic Drugs | chapter = Effect of Hallucinogens on Unconditioned Behavior | series = Current Topics in Behavioral Neurosciences | volume = 36 | pages = 159–199 | date = 2018 | pmid = 28224459 | pmc = 5787039 | doi = 10.1007/7854_2016_466 | isbn = 978-3-662-55878-2 | chapter-url = }}</ref><ref name="SchmidBohn2010" /> These ''N''-methylated tryptamines are well-known for their psychedelic effects, whereas serotonin itself, without [[biotransformation]], does not seem to produce psychedelic effects.<ref name="KozlenkovGonzález-Maeso2013" /><ref name="SchmidBohn2010" /> 5-HTP has not been found to produce psychedelic effects in humans, which has been attributed to the high doses required to produce such effects.<ref name="KozlenkovGonzález-Maeso2013" /><ref name="JasterdelaFuenteRevengaGonzález-Maeso2022" /> The 5-HTP doses that produce the HTR in rodents are orders of magnitude higher than the doses of 5-HTP that have been used safely and therapeutically in humans.<ref name="JasterdelaFuenteRevengaGonzález-Maeso2022" /><ref name="ShaharBotvinnikEsh-Zuntz2022" /> It remains unknown whether 5-HTP can produce psychedelic effects in humans.<ref name="HanksGonzález-Maeso2013">{{cite journal | vauthors = Hanks JB, González-Maeso J | title = Animal models of serotonergic psychedelics | journal = ACS Chem Neurosci | volume = 4 | issue = 1 | pages = 33–42 | date = January 2013 | pmid = 23336043 | pmc = 3547517 | doi = 10.1021/cn300138m | url = | quote = Following these initial studies, it was shown that a large dose of the serotonin precursor 5-hydroxytryptophan (5-HTP) induces head-twitch behavior in mice.32 However, to our knowledge, equivalent doses of 5-HTP have not been tested in healthy volunteers, and therefore, it remains unknown whether 5-HTP is psychedelic in humans. Subsequently, numerous psychedelic compounds were shown to induce head-twitch behavior.27,33−36}}</ref><ref name="ShaharBotvinnikEsh-Zuntz2022" /> The highest dosage of 5-HTP that is known to have been evaluated in humans is about 3,000{{nbsp}}mg per day.<ref name="ShaharBotvinnikEsh-Zuntz2022" /><ref name="TurnerLoftisBlackwell2006" /> [[Serotonin syndrome]] and associated [[hallucination]]s have been reported with [[overdose]] of serotonin-elevating drugs, but psychedelic-like effects have not been reported.<ref name="ShaharBotvinnikEsh-Zuntz2022" />

The lack of the HTR and psychedelic effects with serotonin itself has been attributed to the fact that these effects appear to be dependent on activation of a population of [[intracellular]] 5-HT<sub>2A</sub> receptors expressed in [[Cerebral cortex|cortical]] [[neuron]]s in the [[medial prefrontal cortex]] (mPFC) that lack the [[serotonin transporter]] (SERT) and are inaccessible to serotonin.<ref name="Sapienza2023">{{cite journal | last=Sapienza | first=Jacopo | title=The Key Role of Intracellular 5-HT2A Receptors: A Turning Point in Psychedelic Research? | journal=Psychoactives | volume=2 | issue=4 | date=13 October 2023 | issn=2813-1851 | doi=10.3390/psychoactives2040018 | doi-access=free | pages=287–293}}</ref><ref name="VargasDunlapDong2023">{{cite journal | vauthors = Vargas MV, Dunlap LE, Dong C, Carter SJ, Tombari RJ, Jami SA, Cameron LP, Patel SD, Hennessey JJ, Saeger HN, McCorvy JD, Gray JA, Tian L, Olson DE | title = Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors | journal = Science | volume = 379 | issue = 6633 | pages = 700–706 | date = February 2023 | pmid = 36795823 | pmc = 10108900 | doi = 10.1126/science.adf0435 | bibcode = 2023Sci...379..700V | url = }}</ref> Serotonin itself is too [[hydrophilic]] to enter serotonergic neurons without the SERT, whereas serotonergic psychedelics and serotonin's ''N''-methylated [[metabolite]]s and [[structural analogue|analogue]]s are [[lipophilic]] and readily enter these neurons.<ref name="Sapienza2023" /><ref name="VargasDunlapDong2023" /> These findings may also explain why [[selective serotonin reuptake inhibitor]]s (SSRIs) and related serotonergic agents do not produce psychedelic effects.<ref name="Sapienza2023" />

The properties of 5-HTP in animal [[drug discrimination]] tests have been studied.<ref name="Glennon1988">{{cite journal | vauthors = Glennon RA | title = Site-selective serotonin agonists as discriminative stimuli | journal = Psychopharmacol Ser | volume = 4 | issue = | pages = 15–31 | date = 1988 | pmid = 3293039 | doi = 10.1007/978-3-642-73223-2_2 | url = }}</ref><ref name="BarrettBlackshearSanders-Bush1982">{{cite journal | vauthors = Barrett RJ, Blackshear MA, Sanders-Bush E | title = Discriminative stimulus properties of L-5-hydroxytryptophan: behavioral evidence for multiple serotonin receptors | journal = Psychopharmacology (Berl) | volume = 76 | issue = 1 | pages = 29–35 | date = 1982 | pmid = 6805004 | doi = 10.1007/BF00430750 | url = }}</ref><ref name="CunninghamCallahanAppel1985">{{cite journal | vauthors = Cunningham KA, Callahan PM, Appel JB | title = Differentiation between the stimulus effects of l-5-hydroxytryptophan and LSD | journal = Eur J Pharmacol | volume = 108 | issue = 2 | pages = 179–186 | date = January 1985 | pmid = 3156756 | doi = 10.1016/0014-2999(85)90723-x | url = }}</ref><ref name="FriedmanBarrettSanders-Bush1983">{{cite journal | vauthors = Friedman R, Barrett RJ, Sanders-Bush E | title = Additional evidence that L-5-hydroxytryptophan discrimination models a unique serotonin receptor | journal = Psychopharmacology (Berl) | volume = 80 | issue = 3 | pages = 209–213 | date = 1983 | pmid = 6137018 | doi = 10.1007/BF00436154 | url = }}</ref><ref name="WitkinBradyBarrett1988">{{cite journal | vauthors = Witkin JM, Brady LS, Barrett JE | title = Antagonism by ketanserin of the behavioral effects of quipazine but not l-5-hydroxytryptophan in squirrel monkeys | journal = Psychopharmacology (Berl) | volume = 94 | issue = 3 | pages = 302–305 | date = 1988 | pmid = 3128804 | doi = 10.1007/BF00174679 | url = }}</ref><ref name="WinterRabin1988">{{cite journal | vauthors = Winter JC, Rabin RA | title = A comparison of the discriminative stimulus properties of l-5-hydroxytryptophan in the presence of either citalopram or Ro 4-4602 | journal = Pharmacol Biochem Behav | volume = 30 | issue = 3 | pages = 613–616 | date = July 1988 | pmid = 3264918 | doi = 10.1016/0091-3057(88)90073-1 | url = }}</ref> 5-HTP generalizes with the [[serotonin releasing agent]] [[fenfluramine]] and its cue is markedly potentiated by the [[selective serotonin reuptake inhibitor]] (SSRI) [[fluoxetine]].<ref name="Glennon1988" /><ref name="BarrettBlackshearSanders-Bush1982" /> However, numerous [[serotonin receptor antagonist]]s, including [[methysergide]], [[cyproheptadine]], [[metergoline]], [[methiothepin]] (metitepine), [[ketanserin]], [[pirenperone]], [[pizotifen]], and [[mianserin]], all failed to block the discriminative stimulus properties of 5-HTP.<ref name="Glennon1988" /><ref name="BarrettBlackshearSanders-Bush1982" /><ref name="CunninghamCallahanAppel1985" /><ref name="FriedmanBarrettSanders-Bush1983" /> Conflictingly however, in a subsequent study, pizotifen was able to fully block the discriminative stimulus properties of 5-HTP.<ref name="Glennon1988" /><ref name="FriedmanBarrettSanders-Bush1983" /> The inability of serotonin 5-HT<sub>2A</sub> receptor antagonists to block the discriminative stimulus properties of 5-HTP is in notable contrast to their ability to block the 5-HTP-induced HTR.<ref name="Glennon1992">{{cite book | last=Glennon | first=Richard A. | title=Animal Models of Drug Addiction | chapter=Animal Models for Assessing Hallucinogenic Agents | publisher=Humana Press | publication-place=New Jersey | volume=24 | date=23 October 1992 | isbn=978-0-89603-217-0 | doi=10.1385/0-89603-217-5:345 | url=http://link.springer.com/10.1385/0-89603-217-5:345 | access-date=20 May 2025 | page=345–382}}</ref> 5-HTP only partially substitutes for LSD in drug discrimination tests, whereas LSD and [[quipazine]] fully substitute for 5-HTP.<ref name="CunninghamCallahanAppel1985" /> The full substitution of LSD and quipazine for 5-HTP can be blocked by the serotonin 5-HT<sub>2A</sub> receptor antagonist ketanserin.<ref name="CunninghamCallahanAppel1985" /> The findings of drug discrimination tests suggest that 5-HTP has a more complex or compound discriminative stimulus compared to other agents like LSD and that its stimulus properties may not be readily explained by either the serotonin [[5-HT1 receptor|5-HT<sub>1</sub>]] or [[5-HT2 receptor|5-HT<sub>2</sub> receptor]]s alone.<ref name="Glennon1988" /><ref name="CunninghamCallahanAppel1985" /><ref name="WinterRabin1988" /> Instead, a combination of actions at these and/or other receptors may be involved in its stimulus effects.<ref name="Glennon1988" /><ref name="CunninghamCallahanAppel1985" /><ref name="WinterRabin1988" />

==See also==
* [[α-Methyl-5-hydroxytryptophan]]

==References==
{{Reflist}}

{{Neurotransmitter metabolism intermediates}}
{{Serotonin receptor modulators}}
{{Tryptamines}}

{{DEFAULTSORT:Hydroxytryptophan, 5-}}

[[Category:Alpha-Amino acids]]
[[Category:5-Hydroxytryptamines]]
[[Category:Monoamine precursors]]
[[Category:Serotonin]]