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Names | |
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Preferred IUPAC name
2-(1H-Indol-3-yl)ethan-1-amine | |
Identifiers | |
3D model (JSmol)
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125513 | |
ChEBI | |
ChEMBL | |
ChemSpider | |
DrugBank | |
ECHA InfoCard | 100.000.464 |
KEGG | |
PubChem CID
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UNII | |
CompTox Dashboard (EPA)
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Properties[1] | |
C10H12N2 | |
Molar mass | 160.220 g·mol−1 |
Appearance | white to orange needles |
Melting point | 118˚C |
Boiling point | 137 °C (279 °F; 410 K) (0.15 mmHg) |
negligible solubility in water | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Tryptamine is an indolamine metabolite of the essential amino acid, tryptophan.[2][3] 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).[2] The structure of tryptamine is a shared feature of certain aminergic neuromodulators including melatonin, serotonin, bufotenin and psychedelic derivatives such as dimethyltryptamine (DMT), psilocybin, psilocin and others.[4][5][6] Tryptamine has been shown to activate trace amine-associated receptors expressed in the mammalian brain, and regulates the activity of dopaminergic, serotonergic and glutamatergic systems.[7] [8] In the human gut, symbiotic bacteria convert dietary tryptophan to tryptamine, which activates 5-HT4 receptors and regulates gastrointestinal motility.[3][9][10] Multiple tryptamine-derived drugs have been developed to treat migraines, while trace amine-associated receptors are being explored as a potential treatment target for neuropsychiatric disorders.[11][12][13]
![](https://upload.wikimedia.org/wikipedia/commons/thumb/5/5b/Tryptamine_Alkaloids_2.png/483px-Tryptamine_Alkaloids_2.png)
Natural occurrences
[edit]For a list of plants, fungi and animals containing tryptamines, see List of psychoactive plants and List of naturally occurring tryptamines.
Mammalian brain
[edit]Endogenous levels of tryptamine in the mammalian brain are less than 100 ng per gram of tissue.[14][15] However, elevated levels of trace amines have been observed in patients with certain neuropsychiatric disorders taking medications, such as bipolar depression and schizophrenia.[16]
Mammalian gut microbiome
[edit]Tryptamine is relatively abundant in the gut and feces of humans and rodents.[17][18] Commensal bacteria, including Ruminococcus gnavus and Clostridium sporogenes in the gastrointestinal tract, possess the enzyme tryptophan decarboxylase, which aids in the conversion of dietary tryptophan to tryptamine.[17] Tryptamine is a ligand for gut epithelial serotonin type 4 (5-HT4) receptors and regulates gastrointestinal electrolyte balance through colonic secretions.[18]
Metabolism
[edit]Biosynthesis
[edit]To yield tryptamine in vivo, tryptophan decarboxylase removes the carboxylic acid group on the α-carbon of tryptophan.[19] Synthetic modifications to tryptamine can produce serotonin and melatonin; however, these pathways do not occur naturally as the main pathway for endogenous neurotransmitter synthesis.[20]
![](https://upload.wikimedia.org/wikipedia/commons/thumb/e/ed/Biosynthesis_and_degradation_of_tryptamine.png/482px-Biosynthesis_and_degradation_of_tryptamine.png)
Catabolism
[edit]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.[21]
Mechanisms of action and biological effects
[edit]Neuromodulation
[edit]Tryptamine can weakly activate the trace amine-associated receptor, TAAR1 (hTAAR1 in humans).[22][23][24] 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.[24][25]
hTAAR1
[edit]![](https://upload.wikimedia.org/wikipedia/commons/thumb/0/09/Tryptamine_mechanism_of_action_in_the_human_gut.png/484px-Tryptamine_mechanism_of_action_in_the_human_gut.png)
hTAAR1 is a stimulatory G-protein coupled receptor (GPCR) that is weakly expressed in the intracellular compartment of both pre- and postsynaptic neurons.[26] Tryptamine and other hTAAR1 agonists can increase neuronal firing by inhibiting neurotransmitter recycling through cAMP-dependent phosphorylation of the monoamine reuptake transporter.[27][25] This mechanism increases the amount of neurotransmitter in the synaptic cleft, subsequently increasing postsynaptic receptor binding and neuronal activation.[25] Conversely, when hTAAR1 are colocalized with G protein-coupled inwardly-rectifying potassium channels (GIRKs), receptor activation reduces neuronal firing by facilitating membrane hyperpolarization through the efflux of potassium ions.[25] The balance between the inhibitory and excitatory activity of hTAAR1 activation highlights the role of tryptamine in the regulation of neural activity.[28]
Activation of hTAAR1 is under investigation as a novel treatment for depression, addiction, and schizophrenia.[29] 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 nuclei (DRN).[29] Additionally, the hTAAR1 gene is localized at 6q23.2 on the human chromosome, which is a susceptibility locus for mood disorders and schizophrenia.[30] 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.[28][30]
Gastrointestinal motility
[edit]Tryptamine produced by mutualistic bacteria in the human gut activates serotonin GPCRs ubiquitously expressed along the colonic epithelium.[31] Upon tryptamine binding, the activated 5-HT4 receptor undergoes a conformational change which allows its Gs alpha subunit to exchange GDP for GTP, and its liberation from the 5-HT4 receptor and βγ subunit.[31] GTP-bound Gs activates adenylyl cyclase, which catalyzes the conversion of ATP into cyclic adenosine monophosphate (cAMP).[31] cAMP opens chloride and potassium ion channels to drive colonic electrolyte secretion and promote intestinal motility.[32][33]
Pharmacodynamics
[edit]Tryptamine | Human TAAR1 | Mouse TAAR1 | Rat TAAR | |||
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EC50 | Ki | EC50 | Ki | EC50 | Ki | |
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 |
DMT | >10 | N/A | 1.2 | 3.3 | 1.5 | 22 |
EC50 and Ki values are in micromolar (μM). EC50 reflects the amount
of tryptamine required to elicit 50% of the maximum TAAR1 response. The smaller the Ki value, the stronger the tryptamine binds to the receptor. |
Tryptamine-based therapeutics
[edit]Drug | Mechanism | Treatment | Effect | Structure |
---|---|---|---|---|
Sumatriptan[35] | 5-HT1B and 5-HT1D agonist | Migraine Headaches | Vasoconstriction of brain blood vessels | ![]() |
Rizatriptan[35] | 5-HT1B and 5-HT1D agonist | Migraine Headaches | Vasoconstriction of brain blood vessels | ![]() |
Zolmitriptan[35] | 5-HT1B and 5-HT1D agonist | Migraine Headaches | Vasoconstriction of brain blood vessels | ![]() |
Almotriptan[35] | 5-HT1B and 5-HT1D agonist | Migraine Headaches | Vasoconstriction of brain blood vessels | ![]() |
Eletriptan[35] | 5-HT1B and 5-HT1D agonist | Migraine Headaches | Vasoconstriction of brain blood vessels | ![]() |
Frovatriptan[35] | 5-HT1B and 5-HT1D agonist | Migraine Headaches | Vasoconstriction of brain blood vessels | ![]() |
Naratriptan[35] | 5-HT1B and 5-HT1D agonist | Migraine Headaches | Vasoconstriction of brain blood vessels | ![]() |
See also
[edit]- Tryptophan
- Substituted tryptamines
- Trace amines
- Serotonin receptor agonist
- Human trace amine associated receptor 1
- Neuromodulation
References
[edit]- ^ Lide, D. R., ed. (2005). CRC Handbook of Chemistry and Physics (85th ed.). CRC Press. p. 3-564. ISBN 978-0-8493-0484-2.
- ^ a b "Tryptamine". pubchem.ncbi.nlm.nih.gov. Retrieved 2020-12-01.
- ^ a b Jenkins, Trisha A.; Nguyen, Jason C. D.; Polglaze, Kate E.; Bertrand, Paul P. (2016-01-20). "Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis". Nutrients. 8 (1): 56. doi:10.3390/nu8010056. ISSN 2072-6643. PMC 4728667. PMID 26805875.
- ^ Tylš, Filip; Páleníček, Tomáš; Horáček, Jiří (2014-03-01). "Psilocybin – Summary of knowledge and new perspectives". European Neuropsychopharmacology. 24 (3): 342–356. doi:10.1016/j.euroneuro.2013.12.006. ISSN 0924-977X. PMID 24444771. S2CID 10758314.
- ^ Tittarelli, Roberta; Mannocchi, Giulio; Pantano, Flaminia; Romolo, Francesco Saverio (2015). "Recreational Use, Analysis and Toxicity of Tryptamines". Current Neuropharmacology. 13 (1): 26–46. doi:10.2174/1570159X13666141210222409. ISSN 1570-159X. PMC 4462041. PMID 26074742.
- ^ "The Ayahuasca Phenomenon". MAPS. 21 November 2014. Retrieved 2020-10-03.
- ^ Khan, Muhammad Zahid; Nawaz, Waqas (2016-10-01). "The emerging roles of human trace amines and human trace amine-associated receptors (hTAARs) in central nervous system". Biomedicine & Pharmacotherapy. 83: 439–449. doi:10.1016/j.biopha.2016.07.002. ISSN 0753-3322. PMID 27424325.
- ^ Berry, Mark D.; Gainetdinov, Raul R.; Hoener, Marius C.; Shahid, Mohammed (2017-12-01). "Pharmacology of human trace amine-associated receptors: Therapeutic opportunities and challenges". Pharmacology & Therapeutics. 180: 161–180. doi:10.1016/j.pharmthera.2017.07.002. ISSN 0163-7258. PMID 28723415. S2CID 207366162.
- ^ Bhattarai, Yogesh; Williams, Brianna B.; Battaglioli, Eric J.; Whitaker, Weston R.; Till, Lisa; Grover, Madhusudan; Linden, David R.; Akiba, Yasutada; Kandimalla, Karunya K.; Zachos, Nicholas C.; Kaunitz, Jonathan D. (2018-06-13). "Gut Microbiota-Produced Tryptamine Activates an Epithelial G-Protein-Coupled Receptor to Increase Colonic Secretion". Cell Host & Microbe. 23 (6): 775–785.e5. doi:10.1016/j.chom.2018.05.004. ISSN 1931-3128. PMC 6055526. PMID 29902441.
- ^ Field, Michael (2003). "Intestinal ion transport and the pathophysiology of diarrhea". Journal of Clinical Investigation. 111 (7): 931–943. doi:10.1172/JCI200318326. ISSN 0021-9738. PMC 152597. PMID 12671039.
- ^ "Serotonin Receptor Agonists (Triptans)", LiverTox: Clinical and Research Information on Drug-Induced Liver Injury, Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases, 2012, PMID 31644023, retrieved 2020-10-15
- ^ "New Compound Related to Psychedelic Ibogaine Could Treat Addiction, Depression". UC Davis. 2020-12-09. Retrieved 2020-12-11.
- ^ ServiceDec. 9, Robert F. "Chemists re-engineer a psychedelic to treat depression and addiction in rodents". Science | AAAS. Retrieved 2020-12-11.
{{cite web}}
: CS1 maint: numeric names: authors list (link) - ^ Tittarelli, Roberta; Mannocchi, Giulio; Pantano, Flaminia; Romolo, Francesco Saverio (2015). "Recreational Use, Analysis and Toxicity of Tryptamines". Current Neuropharmacology. 13 (1): 26–46. doi:10.2174/1570159X13666141210222409. ISSN 1570-159X. PMC 4462041. PMID 26074742.
- ^ Berry, Mark D.; Gainetdinov, Raul R.; Hoener, Marius C.; Shahid, Mohammed (2017-12-01). "Pharmacology of human trace amine-associated receptors: Therapeutic opportunities and challenges". Pharmacology & Therapeutics. 180: 161–180. doi:10.1016/j.pharmthera.2017.07.002. ISSN 0163-7258. PMID 28723415. S2CID 207366162.
- ^ Miller, Gregory M. (2011). "The Emerging Role of Trace Amine Associated Receptor 1 in the Functional Regulation of Monoamine Transporters and Dopaminergic Activity". Journal of Neurochemistry. 116 (2): 164–176. doi:10.1111/j.1471-4159.2010.07109.x. ISSN 0022-3042. PMC 3005101. PMID 21073468.
- ^ a b Jenkins, Trisha A.; Nguyen, Jason C. D.; Polglaze, Kate E.; Bertrand, Paul P. (2016-01-20). "Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis". Nutrients. 8 (1): 56. doi:10.3390/nu8010056. ISSN 2072-6643. PMC 4728667. PMID 26805875.
- ^ a b Bhattarai, Yogesh; Williams, Brianna B.; Battaglioli, Eric J.; Whitaker, Weston R.; Till, Lisa; Grover, Madhusudan; Linden, David R.; Akiba, Yasutada; Kandimalla, Karunya K.; Zachos, Nicholas C.; Kaunitz, Jonathan D. (2018-06-13). "Gut Microbiota-Produced Tryptamine Activates an Epithelial G-Protein-Coupled Receptor to Increase Colonic Secretion". Cell Host & Microbe. 23 (6): 775–785.e5. doi:10.1016/j.chom.2018.05.004. ISSN 1931-3128. PMC 6055526. PMID 29902441.
- ^ Tittarelli, Roberta; Mannocchi, Giulio; Pantano, Flaminia; Romolo, Francesco Saverio (2015). "Recreational Use, Analysis and Toxicity of Tryptamines". Current Neuropharmacology. 13 (1): 26–46. doi:10.2174/1570159X13666141210222409. ISSN 1570-159X. PMC 4462041. PMID 26074742.
- ^ "Serotonin Synthesis and Metabolism". Sigma Aldrich. 2020.
- ^ "MetaCyc L-tryptophan degradation VI (via tryptamine)". biocyc.org. Retrieved 2020-12-11.
- ^ Yu, Ai-Ming; Granvil, Camille P.; Haining, Robert L.; Krausz, Kristopher W.; Corchero, Javier; Küpfer, Adrian; Idle, Jeffrey R.; Gonzalez, Frank J. (2003-02-01). "The Relative Contribution of Monoamine Oxidase and Cytochrome P450 Isozymes to the Metabolic Deamination of the Trace Amine Tryptamine". Journal of Pharmacology and Experimental Therapeutics. 304 (2): 539–546. doi:10.1124/jpet.102.043786. ISSN 0022-3565. PMID 12538805. S2CID 18279145.
- ^ Khan, Muhammad Zahid; Nawaz, Waqas (2016-10-01). "The emerging roles of human trace amines and human trace amine-associated receptors (hTAARs) in central nervous system". Biomedicine & Pharmacotherapy. 83: 439–449. doi:10.1016/j.biopha.2016.07.002. ISSN 0753-3322. PMID 27424325.
- ^ a b Zucchi, R; Chiellini, G; Scanlan, T S; Grandy, D K (2006). "Trace amine-associated receptors and their ligands". British Journal of Pharmacology. 149 (8): 967–978. doi:10.1038/sj.bjp.0706948. ISSN 0007-1188. PMC 2014643. PMID 17088868.
- ^ a b c d Miller, Gregory M. (2011). "The Emerging Role of Trace Amine Associated Receptor 1 in the Functional Regulation of Monoamine Transporters and Dopaminergic Activity". Journal of Neurochemistry. 116 (2): 164–176. doi:10.1111/j.1471-4159.2010.07109.x. ISSN 0022-3042. PMC 3005101. PMID 21073468.
- ^ Berry, Mark D.; Gainetdinov, Raul R.; Hoener, Marius C.; Shahid, Mohammed (2017-12-01). "Pharmacology of human trace amine-associated receptors: Therapeutic opportunities and challenges". Pharmacology & Therapeutics. 180: 161–180. doi:10.1016/j.pharmthera.2017.07.002. ISSN 0163-7258. PMID 28723415. S2CID 207366162.
- ^ Jing, Li; Li, Jun-Xu (2015-08-15). "Trace amine-associated receptor 1: a promising target for the treatment of psychostimulant addiction". European Journal of Pharmacology. 761: 345–352. doi:10.1016/j.ejphar.2015.06.019. ISSN 0014-2999. PMC 4532615. PMID 26092759.
- ^ a b Grandy, David K.; Miller, Gregory M.; Li, Jun-Xu (2016-02-01). ""TAARgeting Addiction" The Alamo Bears Witness to Another Revolution". Drug and Alcohol Dependence. 159: 9–16. doi:10.1016/j.drugalcdep.2015.11.014. ISSN 0376-8716. PMC 4724540. PMID 26644139.
- ^ a b Berry, Mark D.; Gainetdinov, Raul R.; Hoener, Marius C.; Shahid, Mohammed (2017-12-01). "Pharmacology of human trace amine-associated receptors: Therapeutic opportunities and challenges". Pharmacology & Therapeutics. 180: 161–180. doi:10.1016/j.pharmthera.2017.07.002. ISSN 0163-7258. PMID 28723415. S2CID 207366162.
- ^ a b Gainetdinov, Raul R.; Hoener, Marius C.; Berry, Mark D. (2018-07-01). "Trace Amines and Their Receptors". Pharmacological Reviews. 70 (3): 549–620. doi:10.1124/pr.117.015305. ISSN 0031-6997. PMID 29941461. S2CID 49411553.
- ^ a b c Bhattarai, Yogesh; Williams, Brianna B.; Battaglioli, Eric J.; Whitaker, Weston R.; Till, Lisa; Grover, Madhusudan; Linden, David R.; Akiba, Yasutada; Kandimalla, Karunya K.; Zachos, Nicholas C.; Kaunitz, Jonathan D. (2018-06-13). "Gut Microbiota-Produced Tryptamine Activates an Epithelial G-Protein-Coupled Receptor to Increase Colonic Secretion". Cell Host & Microbe. 23 (6): 775–785.e5. doi:10.1016/j.chom.2018.05.004. ISSN 1931-3128. PMC 6055526. PMID 29902441.
- ^ Field, Michael (2003). "Intestinal ion transport and the pathophysiology of diarrhea". Journal of Clinical Investigation. 111 (7): 931–943. doi:10.1172/JCI200318326. ISSN 0021-9738. PMC 152597. PMID 12671039.
- ^ "Microbiome-Lax May Relieve Constipation". GEN - Genetic Engineering and Biotechnology News. 2018-06-15. Retrieved 2020-12-11.
- ^ Gainetdinov, Raul R.; Hoener, Marius C.; Berry, Mark D. (2018-07-01). "Trace Amines and Their Receptors". Pharmacological Reviews. 70 (3): 549–620. doi:10.1124/pr.117.015305. ISSN 0031-6997. PMID 29941461. S2CID 49411553.
- ^ a b c d e f g "Serotonin Receptor Agonists (Triptans)", LiverTox: Clinical and Research Information on Drug-Induced Liver Injury, Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases, 2012, PMID 31644023, retrieved 2020-10-15
External links
[edit]- Tryptamine FAQ
- Tryptamine Hallucinogens and Consciousness
- Tryptamind Psychoactives, reference site on tryptamine and other psychoactives.
- Tryptamine (T) entry in TiHKAL • info