View source for Tryptamine

{{about|the specific substance|the class of substances|substituted tryptamine}}
{{short description|Metabolite of the amino acid tryptophan}}
{{chembox
| ImageFile=Tryptamine structure.svg
| ImageSize= 200px
| ImageFile2=Tryptamine-3d-sticks.png
| PIN= 2-(1''H''-Indol-3-yl)ethan-1-amine
| OtherNames=
|Section1={{Chembox Identifiers
| CASNo=61-54-1
| CASNo_Ref = {{cascite|correct|CAS}}
| Beilstein = 125513
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 422ZU9N5TV
| PubChem=1150
| ChEBI = 16765
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 6640
| DrugBank = DB08653
| IUPHAR_ligand = 125
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 1118
| KEGG = C00398
| SMILES = c1ccc2c(c1)c(c[nH]2)CCN
| InChI = 1/C10H12N2/c11-6-5-8-7-12-10-4-2-1-3-9(8)10/h1-4,7,12H,5-6,11H2
| InChIKey = APJYDQYYACXCRM-UHFFFAOYAU
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C10H12N2/c11-6-5-8-7-12-10-4-2-1-3-9(8)10/h1-4,7,12H,5-6,11H2
| StdInChIKey_Ref = {{stdinchicite|correc|chemspider}}
| StdInChIKey = APJYDQYYACXCRM-UHFFFAOYSA-N
 }}
|Section2={{Chembox Properties
|Properties_ref =<ref>{{cite book |title=CRC Handbook of Chemistry and Physics |date=2005 |editor-last=Lide |editor-first=D. R. |edition=85th |publisher=[[CRC Press]] |isbn=978-0-8493-0484-2 |page=3-564}}</ref>
| C=10 | H=12 | N=2
| Appearance=white to orange needles
| Density=
| MeltingPt=118˚C
| BoilingPtC=137
| BoilingPt_notes= (0.15 mmHg)
| Solubility=negligible solubility in water
 }}
|Section3={{Chembox Hazards
| MainHazards=
| FlashPt=
| AutoignitionPt =
 }}
|Section6 = {{Chembox Pharmacology
<!--| Drug_class = [[Serotonin receptor agonist]]; [[Trace amine-associated receptor 1]] (TAAR1) [[agonist]]; [[Serotonin–norepinephrine–dopamine releasing agent]]; [[Serotonergic psychedelic]]; [[Hallucinogen]]--> <!-- Disabled because Chembox Pharmacology Drug_class field is currently broken; see https://en.wikipedia.org/wiki/Template_talk:Chembox#Drug_class_field_not_working (please uncomment field here once this is fixed) -->
| AdminRoutes = [[Intravenous injection|Intravenous]]<ref name="MartinSloan1977" /><ref name="ShulginShulgin1997" /><ref name="MartinSloan1970" />
| Bioavail = Very low
| Excretion = [[Urine]]<ref name="MartinSloan1970" /><ref name="FranzenGross1965" /><ref name="Price1975" />
| DurationOfAction = Very short<ref name="Jones1982" /><ref name="BloughLandavazoDecker2014" /><ref name="ShulginShulgin1997" /><ref name="MartinSloan1970" />
| HalfLife = Very short<ref name="Jones1982" /><ref name="BloughLandavazoDecker2014" /><ref name="ShulginShulgin1997" /><ref name="MartinSloan1970" />
| Metabolism = Very rapid ([[oxidative deamination]] by {{Abbrlink|MAO|monoamine oxidase}})<ref name="Jones1982" /><ref name="BloughLandavazoDecker2014" /><ref name="ShulginShulgin1997" /><ref name="MartinSloan1970" />
| Metabolites = [[Indole-3-acetic acid]] (IAA)
| OnsetOfAction = Very rapid<ref name="Jones1982" /><ref name="BloughLandavazoDecker2014" /><ref name="ShulginShulgin1997" /><ref name="MartinSloan1970" />
| ProteinBound = 
| Legal_status = Legal or unregulated
 }}
}}

'''Tryptamine''' is an [[Indolamines|indolamine]] metabolite of the essential amino acid, [[tryptophan]].<ref name=NML>{{Cite web |title=Tryptamine|url=https://pubchem.ncbi.nlm.nih.gov/compound/1150|access-date=2020-12-01|website=pubchem.ncbi.nlm.nih.gov}}</ref><ref name=":3">{{Cite journal|last1=Jenkins|first1=Trisha A.|last2=Nguyen|first2=Jason C. D.|last3=Polglaze|first3=Kate E.|last4=Bertrand|first4=Paul P.|date=2016-01-20|title=Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis|journal=Nutrients|volume=8|issue=1|page=56|doi=10.3390/nu8010056|issn=2072-6643|pmc=4728667|pmid=26805875|doi-access=free}}</ref> The chemical structure is defined by an [[indole]]—a fused [[benzene]] and [[pyrrole]] ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the first one being the [[heterocyclic]] nitrogen).<ref name="NML"/> The structure of tryptamine is a shared feature of certain aminergic [[Neuromodulation|neuromodulators]] including [[melatonin]], [[serotonin]], [[bufotenin]] and psychedelic derivatives such as [[N,N-Dimethyltryptamine|dimethyltryptamine]] (DMT), [[psilocybin]], [[psilocin]] and [[List of naturally occurring tryptamines|others]].<ref name=":6">{{Cite journal|last1=Tylš|first1=Filip|last2=Páleníček|first2=Tomáš|last3=Horáček|first3=Jiří|date=2014-03-01|title=Psilocybin – Summary of knowledge and new perspectives|url=http://www.sciencedirect.com/science/article/pii/S0924977X13003519|journal=European Neuropsychopharmacology|language=en|volume=24|issue=3|pages=342–356|doi=10.1016/j.euroneuro.2013.12.006|pmid=24444771|s2cid=10758314|issn=0924-977X}}</ref><ref name=":0">{{Cite journal|last1=Tittarelli|first1=Roberta|last2=Mannocchi|first2=Giulio|last3=Pantano|first3=Flaminia|last4=Romolo|first4=Francesco Saverio|date=2015|title=Recreational Use, Analysis and Toxicity of Tryptamines|journal=Current Neuropharmacology|volume=13|issue=1|pages=26–46|doi=10.2174/1570159X13666141210222409|issn=1570-159X|pmc=4462041|pmid=26074742}}</ref><ref name=":5">{{Cite web|title=The Ayahuasca Phenomenon|url=https://maps.org/articles/5408-the-ayahuasca-phenomenon|access-date=2020-10-03|website=MAPS| date=21 November 2014 |language=en-gb}}</ref>

Tryptamine has been shown to activate [[serotonin receptor]]s<ref name="BloughLandavazoDecker2014" /><ref name="Mousseau1993" /> and [[Trace amine-associated receptor|trace amine-associated receptors]] expressed in the mammalian brain, and regulates the activity of [[Dopaminergic pathways|dopaminergic]], [[Serotonin pathway|serotonergic]] and [[Glutamic acid|glutamatergic]] systems.<ref name=":2">{{Cite journal|last1=Khan|first1=Muhammad Zahid|last2=Nawaz|first2=Waqas|date=2016-10-01|title=The emerging roles of human trace amines and human trace amine-associated receptors (hTAARs) in central nervous system|url=http://www.sciencedirect.com/science/article/pii/S075333221630556X|journal=Biomedicine & Pharmacotherapy|language=en|volume=83|pages=439–449|doi=10.1016/j.biopha.2016.07.002|pmid=27424325|issn=0753-3322}}</ref><ref name=":14">{{Cite journal|date=2017-12-01|title=Pharmacology of human trace amine-associated receptors: Therapeutic opportunities and challenges|journal=Pharmacology & Therapeutics|language=en|volume=180|pages=161–180|doi=10.1016/j.pharmthera.2017.07.002|issn=0163-7258|last1=Berry|first1=Mark D.|last2=Gainetdinov|first2=Raul R.|last3=Hoener|first3=Marius C.|last4=Shahid|first4=Mohammed|pmid=28723415|s2cid=207366162|doi-access=free}}</ref> In the human gut, symbiotic bacteria convert dietary tryptophan to tryptamine, which activates [[5-HT4 receptor|5-HT<sub>4</sub>]] receptors and regulates gastrointestinal motility.<ref name=":3" /><ref name=":10">{{Cite journal|last1=Bhattarai|first1=Yogesh|last2=Williams|first2=Brianna B.|last3=Battaglioli|first3=Eric J.|last4=Whitaker|first4=Weston R.|last5=Till|first5=Lisa|last6=Grover|first6=Madhusudan|last7=Linden|first7=David R.|last8=Akiba|first8=Yasutada|last9=Kandimalla|first9=Karunya K.|last10=Zachos|first10=Nicholas C.|last11=Kaunitz|first11=Jonathan D.|date=2018-06-13|title=Gut Microbiota-Produced Tryptamine Activates an Epithelial G-Protein-Coupled Receptor to Increase Colonic Secretion|url= |journal=Cell Host & Microbe|language=en|volume=23|issue=6|pages=775–785.e5|doi=10.1016/j.chom.2018.05.004|issn=1931-3128|pmid=29902441|pmc=6055526}}</ref><ref name=":15">{{Cite journal|last=Field|first=Michael|date=2003|title=Intestinal ion transport and the pathophysiology of diarrhea|journal=Journal of Clinical Investigation|volume=111|issue=7|pages=931–943|doi=10.1172/JCI200318326|issn=0021-9738|pmid=12671039|pmc=152597}}</ref>

Multiple tryptamine-derived drugs have been developed to treat [[Migraine|migraines]], while trace amine-associated receptors are being explored as a potential treatment target for neuropsychiatric disorders.<ref name=":16">{{Citation|title=Serotonin Receptor Agonists (Triptans)|date=2012|url=http://www.ncbi.nlm.nih.gov/books/NBK548713/|work=LiverTox: Clinical and Research Information on Drug-Induced Liver Injury|place=Bethesda (MD)|publisher=National Institute of Diabetes and Digestive and Kidney Diseases|pmid=31644023|access-date=2020-10-15}}</ref><ref name=":7">{{Cite web|date=2020-12-09|title=New Compound Related to Psychedelic Ibogaine Could Treat Addiction, Depression|url=https://www.ucdavis.edu/news/new-compound-related-psychedelic-ibogaine-could-treat-addiction-depression|access-date=2020-12-11|website=UC Davis|language=EN}}</ref><ref name=":8">{{Cite web|last=ServiceDec. 9|first=Robert F.|title=Chemists re-engineer a psychedelic to treat depression and addiction in rodents|url=https://www.science.org/content/article/chemists-re-engineer-psychedelic-treat-depression-and-addiction-rodents|access-date=2020-12-11|website=Science {{!}} AAAS|language=en}}</ref>

== Natural occurrences ==
''For a list of plants, fungi and animals containing tryptamines, see [[List of psychoactive plants]] and [[List of naturally occurring tryptamines]].''

=== Mammalian brain ===
Endogenous levels of tryptamine in the mammalian brain are less than 100&nbsp;ng per gram of tissue.<ref name=":02">{{Cite journal|last1=Tittarelli|first1=Roberta|last2=Mannocchi|first2=Giulio|last3=Pantano|first3=Flaminia|last4=Romolo|first4=Francesco Saverio|date=2015|title=Recreational Use, Analysis and Toxicity of Tryptamines|journal=Current Neuropharmacology|volume=13|issue=1|pages=26–46|doi=10.2174/1570159X13666141210222409|issn=1570-159X|pmc=4462041|pmid=26074742}}</ref><ref name=":142">{{Cite journal|date=2017-12-01|title=Pharmacology of human trace amine-associated receptors: Therapeutic opportunities and challenges|journal=Pharmacology & Therapeutics|language=en|volume=180|pages=161–180|doi=10.1016/j.pharmthera.2017.07.002|issn=0163-7258|last1=Berry|first1=Mark D.|last2=Gainetdinov|first2=Raul R.|last3=Hoener|first3=Marius C.|last4=Shahid|first4=Mohammed|pmid=28723415|s2cid=207366162|doi-access=free}}</ref> However, elevated levels of trace amines have been observed in patients with certain neuropsychiatric disorders taking medications, such as [[Bipolar disorder|bipolar depression]] and [[schizophrenia]].<ref name=":19">{{Cite journal|last=Miller|first=Gregory M.|date=2011|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=164–176|doi=10.1111/j.1471-4159.2010.07109.x|issn=0022-3042|pmc=3005101|pmid=21073468}}</ref>

=== Mammalian gut microbiome ===
Tryptamine is relatively abundant in the [[digestive system|gut]] and feces of humans and rodents.<ref name=":32">{{Cite journal|last1=Jenkins|first1=Trisha A.|last2=Nguyen|first2=Jason C. D.|last3=Polglaze|first3=Kate E.|last4=Bertrand|first4=Paul P.|date=2016-01-20|title=Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis|journal=Nutrients|volume=8|issue=1|page=56|doi=10.3390/nu8010056|issn=2072-6643|pmc=4728667|pmid=26805875|doi-access=free}}</ref><ref name=":102">{{Cite journal|last1=Bhattarai|first1=Yogesh|last2=Williams|first2=Brianna B.|last3=Battaglioli|first3=Eric J.|last4=Whitaker|first4=Weston R.|last5=Till|first5=Lisa|last6=Grover|first6=Madhusudan|last7=Linden|first7=David R.|last8=Akiba|first8=Yasutada|last9=Kandimalla|first9=Karunya K.|last10=Zachos|first10=Nicholas C.|last11=Kaunitz|first11=Jonathan D.|date=2018-06-13|title=Gut Microbiota-Produced Tryptamine Activates an Epithelial G-Protein-Coupled Receptor to Increase Colonic Secretion|url= |journal=Cell Host & Microbe|language=en|volume=23|issue=6|pages=775–785.e5|doi=10.1016/j.chom.2018.05.004|issn=1931-3128|pmid=29902441|pmc=6055526}}</ref> [[Commensalism|Commensal]] bacteria, including ''Ruminococcus gnavus'' and ''[[Clostridium sporogenes]]'' in the [[gastrointestinal tract]], possess the [[enzyme]] tryptophan [[Decarboxylation|decarboxylase]], which aids in the conversion of dietary tryptophan to tryptamine.<ref name=":32" /> Tryptamine is a [[ligand]] for gut epithelial serotonin type 4 (5-HT<sub>4</sub>) receptors and regulates gastrointestinal [[electrolyte]] balance through colonic secretions.<ref name=":102" />

== Metabolism ==

=== Biosynthesis ===
To yield tryptamine ''in vivo'', tryptophan decarboxylase removes the carboxylic acid group on the α-carbon of [[tryptophan]].<ref name=":03">{{Cite journal|last1=Tittarelli|first1=Roberta|last2=Mannocchi|first2=Giulio|last3=Pantano|first3=Flaminia|last4=Romolo|first4=Francesco Saverio|date=2015|title=Recreational Use, Analysis and Toxicity of Tryptamines|journal=Current Neuropharmacology|volume=13|issue=1|pages=26–46|doi=10.2174/1570159X13666141210222409|issn=1570-159X|pmc=4462041|pmid=26074742}}</ref> Synthetic modifications to tryptamine can produce [[serotonin]] and [[melatonin]]; however, these pathways do not occur naturally as the main pathway for endogenous neurotransmitter synthesis.<ref>{{Cite web|date=2020|title=Serotonin Synthesis and Metabolism|url=https://www.sigmaaldrich.com/technical-documents/articles/biology/rbi-handbook/non-peptide-receptors-synthesis-and-metabolism/serotonin-synthesis-and-metabolism.html|website=Sigma Aldrich}}</ref>

=== Catabolism ===
[[Monoamine oxidase|Monoamine oxidases]] A and B are the primary enzymes involved in tryptamine metabolism to produce [[indole-3-acetaldehyde]], however it is unclear which isoform is specific to tryptamine degradation.<ref>{{Cite web|title=MetaCyc L-tryptophan degradation VI (via tryptamine)|url=https://biocyc.org/META/new-image?object=PWY-3181|access-date=2020-12-11|website=biocyc.org}}</ref>

=== Figure ===
[[File:Biosynthesis and degradation of tryptamine.png|thumb|left|550px|Conversion of tryptophan to tryptamine, followed by its degradation to indole-3-acetic acid.]] {{Clear}}

== Biological activity ==
{| class="wikitable floatright" style="font-size:small;"
|+ {{Nowrap|Tryptamine target activities}}
|-
! [[Biological target|Target]] !! [[Affinity (pharmacology)|Affinity]] (K<sub>i</sub>, nM) !! Species
|-
| [[5-HT1A receptor|5-HT<sub>1A</sub>]] || 105 (K<sub>i</sub>)<br />>10,000 ({{Abbrlink|EC<sub>50</sub>|half-maximal effective concentration}}) || Human<br />Human
|-
| [[5-HT1B receptor|5-HT<sub>1B</sub>]] || 36–525 || Human
|-
| [[5-HT1D receptor|5-HT<sub>1D</sub>]] || 23–521 || Human
|-
| [[5-HT1E receptor|5-HT<sub>1E</sub>]] || 2,559 || Human
|-
| [[5-HT1F receptor|5-HT<sub>1F</sub>]] || 2,409 || Human
|-
| [[5-HT2A receptor|5-HT<sub>2A</sub>]] || 89–3,162 (K<sub>i</sub>)<br />7.4–257 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}}) || Human<br />Human
|-
| [[5-HT2B receptor|5-HT<sub>2B</sub>]] || 25–102 (K<sub>i</sub>)<br />29.5 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}}) || Human<br />Human
|-
| [[5-HT2C receptor|5-HT<sub>2C</sub>]] || 46–3,000 (K<sub>i</sub>)<br />45.7 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}}) || Human<br />Human
|-
| [[5-HT3 receptor|5-HT<sub>3</sub>]] || {{Abbr|ND|No data}} || {{Abbr|ND|No data}}
|-
| [[5-HT4 receptor|5-HT<sub>4</sub>]] || >10,000 || Mouse
|-
| [[5-HT5A receptor|5-HT<sub>5A</sub>]] || {{Abbr|ND|No data}} || {{Abbr|ND|No data}}
|-
| [[5-HT6 receptor|5-HT<sub>6</sub>]] || 70–438 || Human
|-
| [[5-HT7 receptor|5-HT<sub>7</sub>]] || 148–158 || Human
|-
| [[Alpha-2A adrenergic receptor|α<sub>2A</sub>]] || 19,000 || Rat
|-
| {{Abbrlink|TAAR1|Human trace amine-associated receptor 1}} || 1,084 (K<sub>i</sub>)<br />2,210–21,000 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}}) || Human<br />Human
|-
| {{Abbrlink|SERT|Serotonin transporter}} || 32.6 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}}) <sup>a</sup> || Rat
|-
| {{Abbrlink|NET|Norepinephrine transporter}} || 716 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}}) <sup>a</sup> || Rat
|-
| {{Abbrlink|DAT|Dopamine transporter}} || 164 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}}) <sup>a</sup> || Rat
|-
| colspan="3" style="width: 1px; background-color:#eaecf0; text-align: center;" | '''Note:''' The smaller the value, the more avidly the compound binds to or activates the site. '''Footnotes:''' <sup>a</sup> = [[Monoamine releasing agent|Neurotransmitter release]]. '''Refs:''' ''Main:'' <ref name="PDSPKiDatabase">{{cite web | title=PDSP Database | website=UNC | url=https://pdsp.unc.edu/databases/pdsp.php?testFreeRadio=testFreeRadio&testLigand=Tryptamine&kiAllRadio=all&doQuery=Submit+Query | language=zu | access-date=7 November 2024}}</ref><ref name="BindingDB">{{cite web | last=Liu | first=Tiqing | title=BindingDB BDBM50024210 1H-indole-3-ethanamine::2-(1H-indol-3-yl)ethanamine::2-(3-indolyl)ethylamine::CHEMBL6640::tryptamine | website=BindingDB | url=https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50024210 | access-date=7 November 2024}}</ref> ''Additional:'' <ref name="GainetdinovHoenerBerry2018" /><ref name="BloughLandavazoDecker2014" /><ref name="BloughLandavazoPartilla2014" /><ref name="PorterBenwellLamb1999">{{cite journal | vauthors = Porter RH, Benwell KR, Lamb H, Malcolm CS, Allen NH, Revell DF, Adams DR, Sheardown MJ | title = Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells | journal = Br J Pharmacol | volume = 128 | issue = 1 | pages = 13–20 | date = September 1999 | pmid = 10498829 | pmc = 1571597 | doi = 10.1038/sj.bjp.0702751 | url = }}</ref>
|}

=== Serotonin receptor agonist ===
Tryptamine is known to act as a [[serotonin receptor]] [[agonist]], although its [[potency (pharmacology)|potency]] is limited by rapid [[catabolism|inactivation]] by [[monoamine oxidase]]s.<ref name="Jones1982" /><ref name="BloughLandavazoDecker2014" /><ref name="Mousseau1993">{{cite journal | vauthors = Mousseau DD | title = Tryptamine: a metabolite of tryptophan implicated in various neuropsychiatric disorders | journal = Metab Brain Dis | volume = 8 | issue = 1 | pages = 1–44 | date = March 1993 | pmid = 8098507 | doi = 10.1007/BF01000528 | url = }}</ref><ref name="AnwarFordBroadley2012">{{cite journal | vauthors = Anwar MA, Ford WR, Broadley KJ, Herbert AA | title = Vasoconstrictor and vasodilator responses to tryptamine of rat-isolated perfused mesentery: comparison with tyramine and β-phenylethylamine | journal = Br J Pharmacol | volume = 165 | issue = 7 | pages = 2191–2202 | date = April 2012 | pmid = 21958009 | pmc = 3413856 | doi = 10.1111/j.1476-5381.2011.01706.x | url = }}</ref><ref name="BradleyHumphreyWilliams1985">{{cite journal | vauthors = Bradley PB, Humphrey PP, Williams RH | title = Tryptamine-induced vasoconstrictor responses in rat caudal arteries are mediated predominantly via 5-hydroxytryptamine receptors | journal = Br J Pharmacol | volume = 84 | issue = 4 | pages = 919–925 | date = April 1985 | pmid = 3159458 | pmc = 1987057 | doi = 10.1111/j.1476-5381.1985.tb17386.x | url = }}</ref> It has specifically been found to act as a [[full agonist]] of the [[serotonin]] [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]] ({{Abbrlink|EC<sub>50</sub>|half-maximal effective concentration}} = 7.36 ± 0.56{{nbsp}}nM; [[intrinsic activity|E<sub>max</sub>]] = 104 ± 4%).<ref name="BloughLandavazoDecker2014" /> Tryptamine was of much lower potency in stimulating the 5-HT<sub>2A</sub> receptor [[β-arrestin]] pathway ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}} = 3,485 ± 234{{nbsp}}nM; E<sub>max</sub> = 108 ± 16%).<ref name="BloughLandavazoDecker2014" /> In contrast to the 5-HT<sub>2A</sub> receptor, tryptamine was found to be inactive at the serotonin [[5-HT1A receptor|5-HT<sub>1A</sub> receptor]].<ref name="BloughLandavazoDecker2014" />

==== Gastrointestinal motility ====
Tryptamine produced by mutualistic bacteria in the human gut activates serotonin GPCRs ubiquitously expressed along the colonic epithelium.<ref name=":103">{{Cite journal|last1=Bhattarai|first1=Yogesh|last2=Williams|first2=Brianna B.|last3=Battaglioli|first3=Eric J.|last4=Whitaker|first4=Weston R.|last5=Till|first5=Lisa|last6=Grover|first6=Madhusudan|last7=Linden|first7=David R.|last8=Akiba|first8=Yasutada|last9=Kandimalla|first9=Karunya K.|last10=Zachos|first10=Nicholas C.|last11=Kaunitz|first11=Jonathan D.|date=2018-06-13|title=Gut Microbiota-Produced Tryptamine Activates an Epithelial G-Protein-Coupled Receptor to Increase Colonic Secretion|url= |journal=Cell Host & Microbe|language=en|volume=23|issue=6|pages=775–785.e5|doi=10.1016/j.chom.2018.05.004|issn=1931-3128|pmid=29902441|pmc=6055526}}</ref> Upon tryptamine binding, the activated 5-HT<sub>4</sub> receptor undergoes a conformational change which allows its [[Gs alpha subunit|G<sub>s</sub> alpha subunit]] to exchange [[Guanosine diphosphate|GDP]] for [[Guanosine triphosphate|GTP]], and its liberation from the 5-HT<sub>4</sub> receptor and βγ subunit.<ref name=":103" /> GTP-bound G<sub>s</sub> activates [[adenylyl cyclase]], which catalyzes the conversion of [[Adenosine triphosphate|ATP]] into [[cyclic adenosine monophosphate]] (cAMP).<ref name=":103" /> cAMP opens chloride and potassium ion channels to drive colonic electrolyte secretion and promote intestinal motility.<ref name=":152">{{Cite journal|last=Field|first=Michael|date=2003|title=Intestinal ion transport and the pathophysiology of diarrhea|journal=Journal of Clinical Investigation|volume=111|issue=7|pages=931–943|doi=10.1172/JCI200318326|issn=0021-9738|pmid=12671039|pmc=152597}}</ref><ref>{{Cite web|date=2018-06-15|title=Microbiome-Lax May Relieve Constipation|url=https://www.genengnews.com/topics/omics/microbiome-lax-may-relieve-constipation/|access-date=2020-12-11|website=GEN - Genetic Engineering and Biotechnology News|language=en-US}}</ref>

[[File:Tryptamine_mechanism_of_action_in_the_human_gut.png|thumb|left|450px|Tryptamine promotes intestinal motility by activating serotonin receptors in the gut to increase colonic secretions.]] {{Clear}}

=== TAAR1 agonist ===
{| class="wikitable floatright" style="font-size:small;"
|+ TAAR1 affinities and activational potencies of tryptamines<ref name="GainetdinovHoenerBerry2018" />
|-
! rowspan="2" | Tryptamine
! colspan="2" | Human TAAR1
! colspan="2" | Mouse TAAR1
! colspan="2" | Rat TAAR1
|-
! EC<sub>50</sub>
! K<sub>i</sub>
! EC<sub>50</sub>
! K<sub>i</sub>
! EC<sub>50</sub>
! K<sub>i</sub>
|-
| Tryptamine
| 21
| N/A
| 2.7
| 1.4
| 0.41
| 0.13
|-
| [[Serotonin]]
| >50
| N/A
| >50
| N/A
| 5.2
| N/A
|-
| [[Psilocin]]
| >30
| N/A
| 2.7
| 17
| 0.92
| 1.4
|-
| [[Dimethyltryptamine]]
| >10
| N/A
| 1.2
| 3.3
| 1.5
| 22
|- class="sortbottom"
| colspan="7" style="width: 1px; background-color:#eaecf0; text-align: center;" | '''Notes:''' (1) [[EC50|EC<sub>50</sub>]] and K<sub>i</sub> values are in micromolar (μM). (2) [[EC50|EC<sub>50</sub>]] reflects the concentration required to elicit 50% of the maximum TAAR1 response. (3) The smaller the K<sub>i</sub> value, the stronger the compound binds to the receptor.
|}

Tryptamine can weakly activate the [[trace amine-associated receptor]], [[TAAR1]] (hTAAR1 in humans).<ref name=":1">{{Cite journal|last1=Yu|first1=Ai-Ming|last2=Granvil|first2=Camille P.|last3=Haining|first3=Robert L.|last4=Krausz|first4=Kristopher W.|last5=Corchero|first5=Javier|last6=Küpfer|first6=Adrian|last7=Idle|first7=Jeffrey R.|last8=Gonzalez|first8=Frank J.|date=2003-02-01|title=The Relative Contribution of Monoamine Oxidase and Cytochrome P450 Isozymes to the Metabolic Deamination of the Trace Amine Tryptamine|url=https://jpet.aspetjournals.org/content/304/2/539|journal=Journal of Pharmacology and Experimental Therapeutics|language=en|volume=304|issue=2|pages=539–546|doi=10.1124/jpet.102.043786|issn=0022-3565|pmid=12538805|s2cid=18279145}}</ref><ref name=":22">{{Cite journal|last1=Khan|first1=Muhammad Zahid|last2=Nawaz|first2=Waqas|date=2016-10-01|title=The emerging roles of human trace amines and human trace amine-associated receptors (hTAARs) in central nervous system|url=http://www.sciencedirect.com/science/article/pii/S075333221630556X|journal=Biomedicine & Pharmacotherapy|language=en|volume=83|pages=439–449|doi=10.1016/j.biopha.2016.07.002|pmid=27424325|issn=0753-3322}}</ref><ref name=":13">{{Cite journal|last1=Zucchi|first1=R|last2=Chiellini|first2=G|last3=Scanlan|first3=T S|last4=Grandy|first4=D K|date=2006|title=Trace amine-associated receptors and their ligands|journal=British Journal of Pharmacology|volume=149|issue=8|pages=967–978|doi=10.1038/sj.bjp.0706948|issn=0007-1188|pmc=2014643|pmid=17088868}}</ref> Limited studies have considered tryptamine to be a trace neuromodulator capable of regulating the activity of neuronal cell responses without binding to the associated postsynaptic receptors.<ref name=":13" /><ref name=":192">{{Cite journal|last=Miller|first=Gregory M.|date=2011|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=164–176|doi=10.1111/j.1471-4159.2010.07109.x|issn=0022-3042|pmc=3005101|pmid=21073468}}</ref>

hTAAR1 is a stimulatory [[G protein-coupled receptor|G-protein coupled receptor]] (GPCR) that is weakly expressed in the intracellular compartment of both pre- and postsynaptic neurons.<ref name=":143">{{Cite journal|date=2017-12-01|title=Pharmacology of human trace amine-associated receptors: Therapeutic opportunities and challenges|journal=Pharmacology & Therapeutics|language=en|volume=180|pages=161–180|doi=10.1016/j.pharmthera.2017.07.002|issn=0163-7258|last1=Berry|first1=Mark D.|last2=Gainetdinov|first2=Raul R.|last3=Hoener|first3=Marius C.|last4=Shahid|first4=Mohammed|pmid=28723415|s2cid=207366162|doi-access=free}}</ref> Tryptamine and other hTAAR1 agonists can increase neuronal firing by inhibiting neurotransmitter recycling through [[Cyclic adenosine monophosphate|cAMP]]-dependent [[phosphorylation]] of the [[Monoamine transporter|monoamine reuptake transporter]].<ref>{{Cite journal|last1=Jing|first1=Li|last2=Li|first2=Jun-Xu|date=2015-08-15|title=Trace amine-associated receptor 1: a promising target for the treatment of psychostimulant addiction|journal=European Journal of Pharmacology|volume=761|pages=345–352|doi=10.1016/j.ejphar.2015.06.019|issn=0014-2999|pmc=4532615|pmid=26092759}}</ref><ref name=":192" /> This mechanism increases the amount of neurotransmitter in the synaptic cleft, subsequently increasing postsynaptic receptor binding and neuronal activation.<ref name=":192" /> Conversely, when hTAAR1 are colocalized with [[G protein-coupled inwardly-rectifying potassium channel|G protein-coupled inwardly-rectifying potassium channels]] (GIRKs), receptor activation reduces neuronal firing by facilitating [[Hyperpolarization (biology)|membrane hyperpolarization]] through the efflux of potassium ions.<ref name=":192" /> The balance between the inhibitory and excitatory activity of hTAAR1 activation highlights the role of tryptamine in the regulation of neural activity.<ref name=":20">{{Cite journal|last1=Grandy|first1=David K.|last2=Miller|first2=Gregory M.|last3=Li|first3=Jun-Xu|date=2016-02-01|title="TAARgeting Addiction" The Alamo Bears Witness to Another Revolution|journal=Drug and Alcohol Dependence|volume=159|pages=9–16|doi=10.1016/j.drugalcdep.2015.11.014|issn=0376-8716|pmc=4724540|pmid=26644139}}</ref>

Activation of hTAAR1 is under investigation as a novel treatment for depression, addiction, and schizophrenia.<ref name=":17">{{Cite journal|date=2017-12-01|title=Pharmacology of human trace amine-associated receptors: Therapeutic opportunities and challenges|journal=Pharmacology & Therapeutics|language=en|volume=180|pages=161–180|doi=10.1016/j.pharmthera.2017.07.002|issn=0163-7258|last1=Berry|first1=Mark D.|last2=Gainetdinov|first2=Raul R.|last3=Hoener|first3=Marius C.|last4=Shahid|first4=Mohammed|pmid=28723415|s2cid=207366162|doi-access=free}}</ref> hTAAR1 is primarily expressed in brain structures associated with dopamine systems, such as the [[ventral tegmental area]] (VTA) and serotonin systems in the [[Dorsal raphe nucleus|dorsal raphe nuclei]] (DRN).<ref name=":17" /> Additionally, the hTAAR1 gene is localized at 6q23.2 on the human chromosome, which is a susceptibility [[Locus (genetics)|locus]] for mood disorders and schizophrenia.<ref name="GainetdinovHoenerBerry2018">{{Cite journal|last1=Gainetdinov|first1=Raul R.|last2=Hoener|first2=Marius C.|last3=Berry|first3=Mark D.|date=2018-07-01|title=Trace Amines and Their Receptors|url=https://pharmrev.aspetjournals.org/content/70/3/549|journal=Pharmacological Reviews|language=en|volume=70|issue=3|pages=549–620|doi=10.1124/pr.117.015305|issn=0031-6997|pmid=29941461|s2cid=49411553|doi-access=free}}</ref> Activation of TAAR1 suggests a potential novel treatment for neuropsychiatric disorders, as TAAR1 agonists produce anti-depressive activity, increased [[cognition]], reduced stress and anti-addiction effects.<ref name=":20" /><ref name="GainetdinovHoenerBerry2018" />

=== Monoamine releasing agent ===
{| class="wikitable floatright" style="font-size:small;"
|+ {{Nowrap|Monoamine release of tryptamine and related agents ({{Abbrlink|EC<sub>50</sub>|Half maximal effective concentration}}, nM)}}
|-
! Compound !! data-sort-type="number" | {{abbrlink|5-HT|Serotonin}} !! data-sort-type="number" | {{abbrlink|NE|Norepinephrine}} !! data-sort-type="number" | {{abbrlink|DA|Dopamine}} !! Ref
|-
| [[Tryptamine]] || 32.6 || 716 || 164 || <ref name="BloughLandavazoDecker2014" /><ref name="BloughLandavazoPartilla2014" />
|-
| [[Serotonin]] || 44.4 || >10000 || ≥1960 || <ref name="RothmanBaumannDersch2001" /><ref name="Blough2008" />
|-
| [[Phenethylamine]] || >10000 || 10.9 || 39.5 || <ref name="ReithBLoughHong2015">{{cite journal | vauthors = Reith ME, Blough BE, Hong WC, Jones KT, Schmitt KC, Baumann MH, Partilla JS, Rothman RB, Katz JL | title = Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter | journal = Drug and Alcohol Dependence | volume = 147 | issue = | pages = 1–19 | date = February 2015 | pmid = 25548026 | pmc = 4297708 | doi = 10.1016/j.drugalcdep.2014.12.005 }}</ref><ref name="Forsyth2012">{{cite web | last=Forsyth | first=Andrea N | title=Synthesis and Biological Evaluation of Rigid Analogues of Methamphetamines | website=ScholarWorks@UNO | date=22 May 2012 | url=https://scholarworks.uno.edu/td/1436/ | access-date=4 November 2024}}</ref><ref name="Blough2008">{{cite book | vauthors = Blough B | chapter = Dopamine-releasing agents | title = Dopamine Transporters: Chemistry, Biology and Pharmacology | pages = 305–320 | date = July 2008 | isbn = 978-0-470-11790-3 | publisher = Wiley | location = Hoboken [NJ] | doi = | url = https://archive.org/details/dopaminetranspor0000unse/page/310/ | archive-url = https://archive.today/20241104022653/https://archive.org/details/dopaminetranspor0000unse/page/310/mode/2up | archive-date = 4 November 2024 | quote = TABLE 11-2 Comparison of the DAT- and NET-Releasing Activity of a Series of Amphetamines [...]}}</ref>
|-
| [[Tyramine]] || 2775 || 40.6 || 119 || <ref name="RothmanBaumannDersch2001" /><ref name="Blough2008" />
|-
| [[N-Methyltryptamine|''N''-Methyltryptamine]] || 22.4 || 733 || 321 || <ref name="BloughLandavazoDecker2014" />
|-
| [[Dimethyltryptamine]] || 114 || 4166 || >10000 || <ref name="BloughLandavazoDecker2014" />
|-
| [[Psilocin]] || 561 || >10000 || >10000 || <ref name="RothmanPartillaBaumann2012">{{cite journal | vauthors = Rothman RB, Partilla JS, Baumann MH, Lightfoot-Siordia C, Blough BE | title = Studies of the biogenic amine transporters. 14. Identification of low-efficacy "partial" substrates for the biogenic amine transporters | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 341 | issue = 1 | pages = 251–262 | date = April 2012 | pmid = 22271821 | pmc = 3364510 | doi = 10.1124/jpet.111.188946 }}</ref><ref name="BloughLandavazoDecker2014" />
|-
| [[Bufotenin]] || 30.5 || >10000 || >10000 || <ref name="BloughLandavazoDecker2014" />
|-
| [[α-Methyltryptamine]] || 21.7–68 || 79–112 || 78.6–180 || <ref name="NagaiNonakaKamimura2007">{{cite journal | vauthors = Nagai F, Nonaka R, Satoh Hisashi Kamimura K | title = The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain | journal = European Journal of Pharmacology | volume = 559 | issue = 2–3 | pages = 132–137 | date = March 2007 | pmid = 17223101 | doi = 10.1016/j.ejphar.2006.11.075 }}</ref>
|-
| [[α-Ethyltryptamine]] || 23.2 || 640 || 232 || <ref name="BloughLandavazoPartilla2014" />
|-
| [[Dextroamphetamine|{{Small|D}}-Amphetamine]] || 698–1765 || 6.6–7.2 || 5.8–24.8 || <ref name="RothmanBaumannDersch2001">{{cite journal | vauthors = Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS | title = Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | journal = Synapse | volume = 39 | issue = 1 | pages = 32–41 | date = January 2001 | pmid = 11071707 | doi = 10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3 | url = }}</ref><ref name="BaumannPartillaLehner2013">{{cite journal | vauthors = Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M, Rothman RB, Goldberg SR, Lupica CR, Sitte HH, Brandt SD, Tella SR, Cozzi NV, Schindler CW | title = Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products | journal = Neuropsychopharmacology | volume = 38 | issue = 4 | pages = 552–562 | year = 2013 | pmid = 23072836 | pmc = 3572453 | doi = 10.1038/npp.2012.204 }}</ref>
|-
| colspan="7" style="width: 1px; background-color:#eaecf0; text-align: center;" | '''Notes:''' The smaller the value, the more strongly the drug releases the neurotransmitter. See also [[Monoamine releasing agent#Activity profiles|Monoamine releasing agent § Activity profiles]] for a larger table with more compounds. '''Refs:''' <ref name="RothmanBaumann2003">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Monoamine transporters and psychostimulant drugs | journal = Eur J Pharmacol | volume = 479 | issue = 1–3 | pages = 23–40 | date = October 2003 | pmid = 14612135 | doi = 10.1016/j.ejphar.2003.08.054 | url = }}</ref><ref name="RothmanBaumann2006">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Therapeutic potential of monoamine transporter substrates | journal = Current Topics in Medicinal Chemistry | volume = 6 | issue = 17 | pages = 1845–1859 | year = 2006 | pmid = 17017961 | doi = 10.2174/156802606778249766 | url = https://zenodo.org/record/1235860 }}</ref>
|}

Tryptamine has been found to act as a [[monoamine releasing agent]].<ref name="Jones1982">{{cite journal | vauthors = Jones RS | title = Tryptamine: a neuromodulator or neurotransmitter in mammalian brain? | journal = Prog Neurobiol | volume = 19 | issue = 1-2 | pages = 117–139 | date = 1982 | pmid = 6131482 | doi = 10.1016/0301-0082(82)90023-5 | url = }}</ref><ref name="BloughLandavazoDecker2014" /><ref name="BloughLandavazoPartilla2014">{{cite journal | vauthors = Blough BE, Landavazo A, Partilla JS, Decker AM, Page KM, Baumann MH, Rothman RB | title = Alpha-ethyltryptamines as dual dopamine-serotonin releasers | journal = Bioorg Med Chem Lett | volume = 24 | issue = 19 | pages = 4754–4758 | date = October 2014 | pmid = 25193229 | pmc = 4211607 | doi = 10.1016/j.bmcl.2014.07.062 | url = }}</ref> It is a releaser of [[serotonin]], [[dopamine]], and [[norepinephrine]], in that order of potency ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}} = 32.6 ± 2.6{{nbsp}}nM, 164 ± 16{{nbsp}}nM, and 716 ± 46{{nbsp}}nM, respectively).<ref name="Jones1982" /><ref name="BloughLandavazoDecker2014" /><ref name="BloughLandavazoPartilla2014" />

=== Monoaminergic activity enhancer ===
Tryptamine is a [[monoaminergic activity enhancer]] (MAE) of [[serotonin]], [[norepinephrine]], and [[dopamine]] in addition to its [[serotonin receptor]] [[agonism]].<ref name="ShimazuMiklya2004">{{cite journal | vauthors = Shimazu S, Miklya I | title = Pharmacological studies with endogenous enhancer substances: beta-phenylethylamine, tryptamine, and their synthetic derivatives | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 28 | issue = 3 | pages = 421–427 | date = May 2004 | pmid = 15093948 | doi = 10.1016/j.pnpbp.2003.11.016 | s2cid = 37564231 }}</ref><ref name="Knoll2003">{{cite journal | vauthors = Knoll J | title = Enhancer regulation/endogenous and synthetic enhancer compounds: a neurochemical concept of the innate and acquired drives | journal = Neurochem Res | volume = 28 | issue = 8 | pages = 1275–1297 | date = August 2003 | pmid = 12834268 | doi = 10.1023/a:1024224311289 | url = }}</ref> That is, it enhances the [[action potential]]-mediated release of these [[monoamine neurotransmitter]]s.<ref name="ShimazuMiklya2004" /><ref name="Knoll2003" /> The MAE actions of tryptamine and other MAEs may be mediated by TAAR1 agonism.<ref name="HarsingKnollMiklya2022">{{cite journal | vauthors = Harsing LG, Knoll J, Miklya I | title = Enhancer Regulation of Dopaminergic Neurochemical Transmission in the Striatum | journal = Int J Mol Sci | volume = 23 | issue = 15 | date = August 2022 | page = 8543 | pmid = 35955676 | pmc = 9369307 | doi = 10.3390/ijms23158543 | doi-access = free | url = }}</ref><ref name="HarsingTimarMiklya2023">{{cite journal | vauthors = Harsing LG, Timar J, Miklya I | title = Striking Neurochemical and Behavioral Differences in the Mode of Action of Selegiline and Rasagiline | journal = Int J Mol Sci | volume = 24 | issue = 17 | date = August 2023 | page = 13334 | pmid = 37686140 | pmc = 10487936 | doi = 10.3390/ijms241713334 | doi-access = free | url = }}</ref> [[Synthetic compound|Synthetic]] and more [[potency (pharmacology)|potent]] MAEs like [[benzofuranylpropylaminopentane]] (BPAP) and [[indolylpropylaminopentane]] (IPAP) have been [[chemical derivative|derived]] from tryptamine.<ref name="ShimazuMiklya2004" /><ref name="Knoll2003" /><ref name="Knoll2001">{{cite journal | vauthors = Knoll J | title = Antiaging compounds: (-)deprenyl (selegeline) and (-)1-(benzofuran-2-yl)-2-propylaminopentane, [(-)BPAP], a selective highly potent enhancer of the impulse propagation mediated release of catecholamine and serotonin in the brain | journal = CNS Drug Rev | volume = 7 | issue = 3 | pages = 317–45 | date = 2001 | pmid = 11607046 | pmc = 6494119 | doi = 10.1111/j.1527-3458.2001.tb00202.x | url = }}</ref><ref name="YonedaMotoSakae2001">{{cite journal | vauthors = Yoneda F, Moto T, Sakae M, Ohde H, Knoll B, Miklya I, Knoll J | title = Structure-activity studies leading to (-)1-(benzofuran-2-yl)-2-propylaminopentane, ((-)BPAP), a highly potent, selective enhancer of the impulse propagation mediated release of catecholamines and serotonin in the brain | journal = Bioorg Med Chem | volume = 9 | issue = 5 | pages = 1197–1212 | date = May 2001 | pmid = 11377178 | doi = 10.1016/s0968-0896(01)00002-5 | url = }}</ref><ref name="KnollYonedaKnoll1999">{{cite journal | vauthors = Knoll J, Yoneda F, Knoll B, Ohde H, Miklya I | title = (-)1-(Benzofuran-2-yl)-2-propylaminopentane, [(-)BPAP], a selective enhancer of the impulse propagation mediated release of catecholamines and serotonin in the brain | journal = British Journal of Pharmacology | volume = 128 | issue = 8 | pages = 1723–1732 | date = December 1999 | pmid = 10588928 | pmc = 1571822 | doi = 10.1038/sj.bjp.0702995 }}</ref>

===Effects in animals and humans===
In a published clinical study, tryptamine, at a total dose of 23 to 277{{nbsp}}mg by [[intravenous therapy|intravenous infusion]], produced [[hallucinogen]]ic effects or perceptual disturbances similar to those of small doses of [[lysergic acid diethylamide]] (LSD).<ref name="MartinSloan1977">{{cite book | last=Martin | first=W. R. | last2=Sloan | first2=J. W. | title=Drug Addiction II | chapter=Pharmacology and Classification of LSD-like Hallucinogens | publisher=Springer Berlin Heidelberg | publication-place=Berlin, Heidelberg | year=1977 | isbn=978-3-642-66711-4 | doi=10.1007/978-3-642-66709-1_3 | page=305–368 | quote=MARTIN and SLOAN (1970) found that intravenously infused tryptamine increased blood pressure, dilated pupils, enhanced the patellar reflex, and produced perceptual distortions. [...] Tryptamine, but not DMT, increases locomotor activity in the mouse, while both antagonize reserpine depression (V ANE et al., 1961). [...] In the rat, tryptamine causes backward locomotion, Straub tail, bradypnea and dyspnea, and clonic convulsions (TEDESCHI et al., 1959). [...] Tryptamine produces a variety of changes in the cat causing signs of sympathetic activation including mydriasis, retraction of nictitating membrane, piloerection, motor signs such as extension of limbs and convulsions and affective changes such as hissing and snarling (LAIDLAW, 1912). [...]}}</ref><ref name="ShulginShulgin1997">{{cite book | last=Shulgin | first=A. | last2=Shulgin | first2=A. | title=Tihkal: The Continuation | publisher=Transform Press | year=1997 | isbn=978-0-9630096-9-2 | url=https://books.google.com/books?id=jl_ik66IumUC | access-date=17 August 2024 | page= | at=[https://www.erowid.org/library/books_online/tihkal/tihkal53.shtml #53. T] | quote = (with 250 mg, intravenously) "Tryptamine was infused intravenously over a period of up to 7.5 minutes. Physical changes included an increases in blood pressure, in the amplitude of the patellar reflex, and in pupillary diameter. The subjective changes are not unlike those seen with small doses of LSD. A point-by-point comparison between the tryptamine and LSD syndromes reveals a close similarity which is consistent with the hypothesis that tryptamine and LSD have a common mode of action."}}</ref><ref name="BloughLandavazoDecker2014">{{cite journal | vauthors = Blough BE, Landavazo A, Decker AM, Partilla JS, Baumann MH, Rothman RB | title = Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes | journal = Psychopharmacology (Berl) | volume = 231 | issue = 21 | pages = 4135–4144 | date = October 2014 | pmid = 24800892 | pmc = 4194234 | doi = 10.1007/s00213-014-3557-7 | url = | quote = [Tryptamine (T): [...] Psychoactive effects: Psychoactive, short acting due to metabolism, increased blood pressure, similar to LSD}}</ref><ref name="MartinSloan1970">{{cite journal | vauthors = Martin WR, Sloan JW | title = Effects of infused tryptamine in man | journal = Psychopharmacologia | volume = 18 | issue = 3 | pages = 231–237 | date = 1970 | pmid = 4922520 | doi = 10.1007/BF00412669 | url = }}</ref> It also produced other LSD-like effects, including [[pupil dilation]], increased [[blood pressure]], and increased force of the [[patellar reflex]].<ref name="MartinSloan1977" /><ref name="BloughLandavazoDecker2014" /><ref name="ShulginShulgin1997" /><ref name="MartinSloan1970" /> Tryptamine produced [[side effect]]s including [[nausea]], [[vomiting]], [[dizziness]], [[tingling]] sensations, [[sweating]], and bodily heaviness among others as well.<ref name="MartinSloan1977" /><ref name="MartinSloan1970" /> Conversely, there were no changes in [[heart rate]] or [[respiratory rate]].<ref name="MartinSloan1970" /> The [[onset of action|onset]] of the effects was rapid and the [[duration of action|duration]] was very short.<ref name="Jones1982" /><ref name="BloughLandavazoDecker2014" /><ref name="ShulginShulgin1997" /><ref name="MartinSloan1970" /> This can be attributed to the very rapid [[drug metabolism|metabolism]] of tryptamine by [[monoamine oxidase]] (MAO) and its very short [[elimination half-life]].<ref name="Jones1982" /><ref name="BloughLandavazoDecker2014" /><ref name="ShulginShulgin1997" /><ref name="MartinSloan1970" />

In animals, tryptamine, alone and/or in combination with a [[monoamine oxidase inhibitor]] (MAOI), produces behavioral changes such as [[hyperlocomotion]] and reversal of [[reserpine]]-induced [[hypoactivity|behavioral depression]].<ref name="MartinSloan1977" /><ref name="Jones1982" /><ref name="KellarCascio1986" /><ref name="MurphyTamarkinGarrick1985" /> In addition, it produces effects like [[hyperthermia]], [[tachycardia]], [[myoclonus]], and [[seizure]]s or [[convulsion]]s, among others.<ref name="MartinSloan1977" /><ref name="Jones1982" /><ref name="KellarCascio1986" /><ref name="MurphyTamarkinGarrick1985" /> Findings on tryptamine and the [[head-twitch response]] in rodents are mixed, with some studies reporting no effect,<ref name="Jones1981" /><ref name="YamadaSugimotoHorisaka1987">{{cite journal | vauthors = Yamada J, Sugimoto Y, Horisaka K | title = The behavioural effects of intravenously administered tryptamine in mice | journal = Neuropharmacology | volume = 26 | issue = 1 | pages = 49–53 | date = January 1987 | pmid = 3561719 | doi = 10.1016/0028-3908(87)90043-8 | url = }}</ref> some reporting induction of head twitches by tryptamine,<ref name="HaberzettlBertFink2013">{{cite journal | vauthors = Haberzettl R, Bert B, Fink H, Fox MA | title = Animal models of the serotonin syndrome: a systematic review | journal = Behav Brain Res | volume = 256 | issue = | pages = 328–345 | date = November 2013 | pmid = 24004848 | doi = 10.1016/j.bbr.2013.08.045 | url = | doi-access = free }}</ref><ref name="SugimotoYamadaHorisaka1986">{{cite journal | vauthors = Sugimoto Y, Yamada J, Horisaka K | title = Effect of tryptamine on the behavior of mice | journal = J Pharmacobiodyn | volume = 9 | issue = 1 | pages = 68–73 | date = January 1986 | pmid = 2940357 | doi = 10.1248/bpb1978.9.68 | url = }}</ref> and others reporting that tryptamine actually antagonized [[5-hydroxytryptophan]] (5-HTP)-induced head twitches.<ref name="KellarCascio1986" /><ref name="Jones1981">{{cite journal | vauthors = Jones RS | title = In vivo pharmacological studies on the interactions between tryptamine and 5-hydroxytryptamine | journal = Br J Pharmacol | volume = 73 | issue = 2 | pages = 485–493 | date = June 1981 | pmid = 6972243 | pmc = 2071674 | doi = 10.1111/j.1476-5381.1981.tb10447.x | url = }}</ref> Head twitches in rodents are a behavioral proxy of psychedelic-like 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">{{cite book | last=Kozlenkov | first=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 | page=253–277}}</ref> Many of the effects of tryptamine can be reversed by [[serotonin receptor antagonist]]s like [[metergoline]], [[metitepine]] (methiothepin), and [[cyproheptadine]].<ref name="Jones1982" /><ref name="KellarCascio1986" /><ref name="MurphyTamarkinGarrick1985" /><ref name="MartinSloan1977" /> Conversely, the effects of tryptamine in animals are profoundly augmented by MAOIs due to inhibition of its metabolism.<ref name="Jones1982" /><ref name="MurphyTamarkinGarrick1985" /><ref name="MartinSloan1977" />

Tryptamine seems to also elevate [[prolactin]] and [[cortisol]] levels in animals and/or humans.<ref name="MurphyTamarkinGarrick1985" />

The {{Abbrlink|LD<sub>50</sub>|median lethal dose}} values of tryptamine in animals include 100{{nbsp}}mg/kg i.p. in mice, 500{{nbsp}}mg/kg s.c. in mice, and 223{{nbsp}}mg/kg i.p. in rats.<ref name="PubChem" />

==Pharmacokinetics==
Tryptamine produced [[endogenous]]ly or [[peripheral administration|administered peripherally]] is readily able to cross the [[blood–brain barrier]] and enter the [[central nervous system]].<ref name="MurphyTamarkinGarrick1985">{{cite book | last=Murphy | first=D. L. | last2=Tamarkin | first2=L. | last3=Garrick | first3=N. A. | last4=Taylor | first4=P. L. | last5=Markey | first5=S. P. | title=Neuropsychopharmacology of the Trace Amines | chapter=Trace Indoleamines in the Central Nervous System | publisher=Humana Press | publication-place=Totowa, NJ | year=1985 | isbn=978-1-4612-9397-2 | doi=10.1007/978-1-4612-5010-4_36 | page=343–360}}</ref><ref name="KellarCascio1986">{{cite book | last=Kellar | first=Kenneth J. | last2=Cascio | first2=Caren S. | title=Receptor Binding | chapter=Tryptamine and Phenylethylamine Recognition Sites in Brain | publisher=Humana Press | publication-place=New Jersey | isbn=0-89603-078-4 | doi=10.1385/0-89603-078-4:119 | page=119–138}}</ref> This is in contrast to [[serotonin]], which is [[peripherally selective drug|peripherally selective]].<ref name="MurphyTamarkinGarrick1985" />

Tryptamine is [[drug metabolism|metabolized]] by [[monoamine oxidase]] (MAO) to form [[indole-3-acetic acid]] (IAA).<ref name="MurphyTamarkinGarrick1985" /><ref name="Jones1982" /><ref name="KellarCascio1986" /> Its metabolism is described as extremely rapid and its [[elimination half-life]] and [[duration of action|duration]] as very short.<ref name="Jones1982" /><ref name="BloughLandavazoDecker2014" /><ref name="ShulginShulgin1997" /><ref name="MartinSloan1970" /> In addition, its duration is described as shorter than that of [[dimethyltryptamine]] (DMT).<ref name="MartinSloan1977" /> Brain tryptamine levels are increased up to 300-fold by MAOIs in animals.<ref name="KellarCascio1986" /> In addition, the effects of [[exogenous]] tryptamine are strongly augmented by [[monoamine oxidase inhibitor]]s (MAOIs).<ref name="Jones1982" /><ref name="KellarCascio1986" />

Tryptamine is [[excretion|excreted]] in [[urine]] and its rate of urinary excretion has been reported to be [[pH]]-dependent.<ref name="MartinSloan1970" /><ref name="FranzenGross1965">{{cite journal | vauthors = Franzen F, Gross H | title = Tryptamine, N,N-dimethyltryptamine, N,N-dimethyl-5-hydroxytryptamine and 5-methoxytryptamine in human blood and urine | journal = Nature | volume = 206 | issue = 988 | pages = 1052 | date = June 1965 | pmid = 5839067 | doi = 10.1038/2061052a0 | url = }}</ref><ref name="Price1975">{{cite journal | vauthors = Price J | title = The dependence of tryptamine excretion on urinary pH | journal = Clin Chim Acta | volume = 65 | issue = 3 | pages = 339–342 | date = December 1975 | pmid = 1161 | doi = 10.1016/0009-8981(75)90259-4 | url = }}</ref>

==Chemistry==
Tryptamine is a [[substituted tryptamine]] [[chemical derivative|derivative]] and [[trace amine]] and is [[structural analog|structurally related]] to the [[amino acid]] [[tryptophan]].

The experimental [[partition coefficient|log P]] of tryptamine is 1.55.<ref name="PubChem">{{cite web | title=Tryptamine | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/1150 | access-date=7 November 2024}}</ref>

===Derivatives===
{{Main|Substituted tryptamine}}

The [[endogenous]] [[monoamine neurotransmitter]]s [[serotonin]] (5-hydroxytryptamine or 5-HT) and [[melatonin]] (5-methoxy-''N''-acetyltryptamine), as well as trace amines like [[N-methyltryptamine|''N''-methyltryptamine]] (NMT), [[dimethyltryptamine|''N'',''N''-dimethyltryptamine]] (DMT), and [[bufotenin]] (''N'',''N''-dimethylserotonin), are [[chemical derivative|derivative]]s of tryptamine.

A variety of drugs, including both [[natural product|naturally occurring]] and [[pharmaceutical drug|pharmaceutical]] substances, are derivatives of tryptamine. These include the tryptamine psychedelics like [[psilocybin]], [[psilocin]], DMT, and [[5-MeO-DMT]]; tryptamine [[stimulant]]s, [[entactogen]]s, psychedelics, and/or [[antidepressant]]s like [[α-methyltryptamine]] (αMT) and [[α-ethyltryptamine]] (αET); [[triptan]] [[antimigraine agent]]s like [[sumatriptan]]; certain [[antipsychotic]]s like [[oxypertine]]; and the [[sleep aid]] [[melatonin (medication)|melatonin]].

[[File:Tryptamine Alkaloids 2.png|thumb|483x483px|All tryptamine derivatives possess a modified 2-aminoethyl group and/or the addition of a substituent on the indole.]]

Various other drugs, including [[ergoline]]s and [[lysergamide]]s like the psychedelic [[lysergic acid diethylamide]] (LSD), the antimigraine agents [[ergotamine]], [[dihydroergotamine]], and [[methysergide]], and the [[antiparkinsonian agent]]s [[bromocriptine]], [[cabergoline]], [[lisuride]], and [[pergolide]]; [[β-carboline]]s like [[harmine]] (some of which are [[monoamine oxidase inhibitor]]s (MAOIs)); [[Iboga-type alkaloid|''Iboga'' alkaloid]]s like the [[hallucinogen]] [[ibogaine]]; [[yohimban]]s like the [[alpha-2 blocker|α<sub>2</sub> blocker]] [[yohimbine]]; antipsychotics like [[ciclindole]] and [[flucindole]]; and the MAOI antidepressant [[metralindole]], can all be thought of as [[cyclic compound|cyclized]] tryptamine derivatives.

Drugs very closely related to tryptamines, but technically not tryptamines themselves, include certain triptans like [[avitriptan]] and [[naratriptan]]; the antipsychotics [[sertindole]] and [[tepirindole]]; and the MAOI antidepressants [[pirlindole]] and [[tetrindole]].

==References==
{{Reflist|2}}

== External links ==
* [https://www.erowid.org/psychoactives/faqs/faqs_tryptamine.shtml Tryptamine FAQ]
* [http://www.tryptamind.com/tryptamine.html Tryptamine Hallucinogens and Consciousness]
* [http://www.tryptamind.com/ Tryptamind Psychoactives], reference site on tryptamine and other psychoactives.
* [http://isomerdesign.com/PiHKAL/read.php?domain=tk&id=53 Tryptamine (T) entry in TiHKAL • info]

{{Neurotransmitters}}
{{Navboxes
| title = [[Biological activity|Biological activities]]
| titlestyle = background:#ccccff
| list1 =
{{Serotonin receptor modulators}}
{{TAAR ligands}}
{{Monoamine releasing agents}}
{{Monoaminergic activity enhancers}}
}}
{{Tryptamines}}
{{Chocolate}}

[[Category:5-HT2A agonists]]
[[Category:Biogenic amines]]
[[Category:Monoaminergic activity enhancers]]
[[Category:Serotonin receptor agonists]]
[[Category:Serotonin-norepinephrine-dopamine releasing agents]]
[[Category:TAAR1 agonists]]
[[Category:Trace amines]]
[[Category:Tryptamines| ]]