N-Methyltryptamine

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Wikipedia

N-Methyltryptamine
Clinical data
Other namesNMT; Methyltryptamine; N-MT; Monomethyltryptamine; Dipterine; PAL-152; PAL152
Routes of
administration		Smoking, oral (with an MAOITooltip monoamine oxidase inhibitor)[1][2][3]
Drug classNon-selective serotonin receptor agonist; Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen
Legal status
Legal status
Pharmacokinetic data
Duration of actionSeconds to minutes[1][2][3]
Identifiers
  • 2-(1H-indol-3-yl)-N-methylethan-1-amine
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.000.462 Edit this at Wikidata
Chemical and physical data
FormulaC11H14N2
Molar mass174.247 g·mol−1
3D model (JSmol)
Melting point87 to 89 °C (189 to 192 °F)
  • CNCCc1c[nH]c2ccccc12
  • InChI=1S/C11H14N2/c1-12-7-6-9-8-13-11-5-3-2-4-10(9)11/h2-5,8,12-13H,6-7H2,1H3 checkY
  • Key:NCIKQJBVUNUXLW-UHFFFAOYSA-N checkY
  (verify)

N-Methyltryptamine (NMT), also known as monomethyltryptamine, is a chemical compound of the tryptamine family and a naturally occurring compound found in the human body and certain plants.

It is biosynthesized in humans from tryptamine by certain N-methyltransferase enzymes, such as indolethylamine N-methyltransferase.[4][5] It is a known component in human urine.[6] NMT is an alkaloid derived from L-tryptophan that has been found in the bark, shoots and leaves of several plant genera, including Virola, Acacia, Mimosa, and Desmanthus—often together with the related compounds N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT).[7]

NMT acts as a serotonin receptor agonist and serotonin releasing agent[8] and is said to produce hallucinogenic effects in humans.[1][2][3]

Use and effects

Orally administered NMT appears to produce no psychoactive effects, likely as a result of extensive first-pass metabolism.[9]

According to Roger W. Brimblecombe and colleagues, NMT is inactive in humans, with few details provided.[10] On the other hand, according to Alexander Shulgin and others, NMT is active via non-oral routes.[1][2][3] It has been said to produce psychedelic effects at doses of 50 to 120 mg by smoking or vaporization, with a duration of seconds to minutes.[1][2][3] Based on preliminary reports, NMT is reported to produce visuals, but its effects are described as primarily spatial in nature, among other effects.[1][2][3]

NMT has also been reported to be orally active in combination with a monoamine oxidase inhibitor (MAOI).[2][3]

Interactions

Pharmacology

Pharmacodynamics

NMT activities
TargetAffinity (Ki, nM)
5-HT1AIA
5-HT2A51 (EC50Tooltip half-maximal effective concentration)
96% (EmaxTooltip maximal efficacy)
SERT22a (EC50)
NETTooltip Norepinephrine transporter 733a (EC50)
DATTooltip Dopamine transporter 321a (EC50)
Notes: The smaller the value, the more avidly the drug interacts with the site. Footnotes: a = Neurotransmitter release. Sources: [8]

NMT is known to act as a potent serotonin 5-HT2A receptor full agonist.[8] It has been reported to be inactive in activating the β-arrestin2 pathway of the receptor and hence appears to be a biased agonist of the serotonin 5-HT2A receptor.[8][11] The drug does not seem to be an agonist of the serotonin 5-HT1A receptor.[8]

In addition to its serotonin 5-HT2A receptor agonism, NMT is a potent serotonin releasing agent.[8] It also releases dopamine and norepinephrine much more weakly (14- and 33-fold less than for serotonin, respectively).[8]

NMT has also been evaluated for binding affinity at the sigma σ1 and sigma σ2 receptors.[12] It's affinity towards both sigma receptors is intermediate between the unmethylated tryptamine and the fully dimethylated DMT.[12]

Pharmacokinetics

NMT undergoes oxidative deamination by monoamine oxidase (MAO), particularly MAO-A, which preferentially metabolizes serotonin and tryptamine derivatives. The intermediate methylation state of NMT makes it a substrate for further N-methylation to DMT by amine N-methyltransferase (INMT).

Chemistry

Synthesis

The chemical synthesis of NMT has been described.[1]

Analogues

Analogues of NMT include N-ethyltryptamine (NET), methylethyltryptamine (MET), and dimethyltryptamine (DMT), among others.[1]

Natural occurrence

NMT is naturally occurring in Acacia species like Acacia confusa (1.63%; Buchanan et al., 2007), Acacia obtusifolia (up to two-thirds of total alkaloid content), and Acacia simplicifolia (A. simplex; 1.44% in bark, 0.29% twigs; Pouet et al., 1976) and Desmanthus illinoensis (major component seasonally).

Society and culture

United States

In the United States, NMT is considered a schedule 1 controlled substance as an positional isomer of α-methyltryptamine (AMT).[13]

See also

References

  1. 1 2 3 4 5 6 7 8 Shulgin A, Shulgin A (1997). TiHKAL: The Continuation. Berkeley: Transform Press. To my knowledge there have been no reports of oral activity of NMT, although its wide availability from botanic sources has encouraged some explorers to assay it. I have had one report that the smoking of 50–100 mg gave visuals that lasted for maybe 15 seconds.
  2. 1 2 3 4 5 6 7 Nen (4 December 2011). Entheogenic effects of NMT from Acacia. Entheogenesis Australis (EGA) Conference, Victoria, Australia, 2–5 December 2011 (PDF). Archived from the original on 5 April 2025. Retrieved 15 April 2025.
  3. 1 2 3 4 5 6 7 Nen (13 July 2013). NMT: A Spatial Hallucinogen With Therapeutic Applications. Breaking Convention: The Second Multidisciplinary Conference on Psychedelic Consciousness, University of Greenwich, London, 12–14 July 2013.
  4. ↑ Lindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel GPCR family". Trends in Pharmacological Sciences. 26 (5): 274–281. doi:10.1016/j.tips.2005.03.007. PMID 15860375.
  5. ↑ Burchett SA, Hicks TP (August 2006). "The mysterious trace amines: protean neuromodulators of synaptic transmission in mammalian brain". Progress in Neurobiology. 79 (5–6): 223–246. doi:10.1016/j.pneurobio.2006.07.003. PMID 16962229. S2CID 10272684.
  6. ↑ Forsström T, Tuominen J, Karkkäinen J (2001). "Determination of potentially hallucinogenic N-dimethylated indoleamines in human urine by HPLC/ESI-MS-MS". Scandinavian Journal of Clinical and Laboratory Investigation. 61 (7): 547–56. doi:10.1080/003655101753218319. PMID 11763413. S2CID 218987277.
  7. ↑ Ott, Jonathan (1996). Pharmacotheon: Entheogenic Drugs, Their Plant Sources and History. Natural Products Company. ISBN 978-0-9614234-8-3.
  8. 1 2 3 4 5 6 7 Blough BE, Landavazo A, Decker AM, Partilla JS, Baumann MH, Rothman RB (October 2014). "Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes". Psychopharmacology (Berl). 231 (21): 4135–4144. doi:10.1007/s00213-014-3557-7. PMC 4194234. PMID 24800892.
  9. ↑ Foye WO, Lemke TL, Williams DA (2002). "Hallucinogens, Stimulatants, and Drugs of Abuse". Foye's Principles of Medicinal Chemistry (5th ed.). Lippincott Williams & Wilkins. p. 439. ISBN 9780683307375.
  10. ↑ Brimblecombe RW, Pinder RM (1975). "Indolealkylamines and Related Compounds". Hallucinogenic Agents. Bristol: Wright-Scientechnica. pp. 98–144. ISBN 978-0-85608-011-1. OCLC 2176880. OL 4850660M. N-Monoalkyltryptamines resemble the unsubstituted tryptamines in being good substrates for amine oxidases (Erspamer, 1955), a property which is reflected in their relatively poor hallucinogenic activity as compared to their N,N-dialkyl analogues. Thus, neither tryptamine nor its N-methyl derivative, both of which are oxidatively deaminated in rats to free (and conjugated) indole-3-acetic acids to the extent of 84·6 and 35·7 per cent respectively, produce behavioural changes in animals or man, whereas N,N-dimethyltryptamine, which is but little affected by amine oxidases, is a potent hallucinogen.
  11. ↑ Schmid CL, Bohn LM (October 2010). "Serotonin, But Not N-Methyltryptamines, Activates the Serotonin 2A Receptor Via a β-Arrestin2/Src/Akt Signaling Complex In Vivo". The Journal of Neuroscience. 30 (40): 13513–13524. doi:10.1523/JNEUROSCI.1665-10.2010. ISSN 0270-6474. PMC 3001293. PMID 20926677.
  12. 1 2 Fontanilla D, Johannessen M, Hajipour AR, Cozzi NV, Jackson MB, Ruoho AE (February 2009). "The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator". Science. 323 (5916): 934–937. doi:10.1126/science.1166127. ISSN 0036-8075. PMC 2947205. PMID 19213917.
  13. ↑ "Orange Book - List of Controlled Substances and Regulated Chemicals" (PDF). U.S. Department of Justice Diversion Control Division. August 2023. Archived (PDF) from the original on September 6, 2023.