N-Methyltryptamine

Last updated
N-Methyltryptamine
NMT structure.svg
NMT 3D.png
Clinical data
Other namesNMT; Methyltryptamine; N-MT; Monomethyltryptamine; Dipterine; PAL-152; PAL152
Routes of
administration 		Smoking, oral (with an MAOI Tooltip monoamine oxidase inhibitor) [1] [2] [3]
Drug class Non-selective serotonin receptor agonist; Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen
Legal status
Legal status
Pharmacokinetic data
Duration of action Seconds 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 InfoCard 100.000.462 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C11H14N2
Molar mass 174.247 g·mol−1
3D model (JSmol)
Melting point 87 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 Yes check.svgY
  • Key:NCIKQJBVUNUXLW-UHFFFAOYSA-N Yes check.svgY
   (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.

Contents

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-HT1A IA
5-HT2A 51 (EC50 Tooltip half-maximal effective concentration)
96% (Emax Tooltip maximal efficacy)
SERT 22a (EC50)
NET Tooltip Norepinephrine transporter733a (EC50)
DAT Tooltip Dopamine transporter321a (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 is not 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. 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) 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. ↑ 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.