5-Methyltryptamine

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5-Methyltryptamine
5-Methyltryptamine.svg
Clinical data
Other names5-MeT; 5-Me-T; 5-Methyl-T; 5-MT; PAL-22; PAL22; NSC-90805; NSC90805
Drug class Serotonin receptor agonist; Serotonin releasing agent
Identifiers
  • 2-(5-methyl-1H-indol-3-yl)ethanamine
CAS Number
PubChem CID
ChemSpider
ChEBI
ChEMBL
Chemical and physical data
Formula C11H14N2
Molar mass 174.247 g·mol−1
3D model (JSmol)
  • CC1=CC2=C(C=C1)NC=C2CCN
  • InChI=1S/C11H14N2/c1-8-2-3-11-10(6-8)9(4-5-12)7-13-11/h2-3,6-7,13H,4-5,12H2,1H3
  • Key:PYOUAIQXJALPKW-UHFFFAOYSA-N

5-Methyltryptamine (5-MeT, 5-Me-T) is a non-selective serotonin receptor agonist and serotonin releasing agent of the tryptamine family that has been used in scientific research. [1] [2] It is related to other 5-substituted tryptamines such as serotonin (5-hydroxytryptamine; 5-HT) and 5-methoxytryptamine (5-MeO-T). [1] [2] The compound is also a positional isomer of N-methyltryptamine (NMT). [1]

Contents

Pharmacology

5-MeT is known to act as a potent serotonin 5-HT2A receptor full agonist, with an EC50 Tooltip half-maximal effective concentration of 6.00 nM and an Emax Tooltip maximal efficacy of 100%. [1] In addition, it is known to be a ligand of the serotonin 5-HT1A [3] and 5-HT2B receptors [2] and an agonist of the serotonin 5-HT1D [4] [5] and 5-HT2C receptors. [6] [7] Similarly to tryptamine and 5-MeO-T, but in contrast to serotonin, 5-MeT shows very low potency as an agonist of the serotonin 5-HT3 receptor (EC50 = 60,000 nM). [8]

In addition to acting as an agonist of many serotonin receptors, 5-MeT is a monoamine releasing agent (MRA), with complete selectivity for induction of serotonin release over induction of dopamine and norepinephrine release (EC50 = 139 nM, >10,000 nM, and >10,000 nM, respectively, in rat brain synaptosomes). [1] However, its potency for induction of serotonin release in this system is 23-fold lower than its potency as a serotonin 5-HT2A receptor agonist. [1]

Tryptamines without substitutions at the amine or alpha carbon, such as tryptamine, serotonin, and 5-MeO-T, are known to be very rapidly metabolized and thereby inactivated by monoamine oxidase A (MAO-A) in vivo and to have very short elimination half-lives. [9] [10] [11] [12] [13] [2] [14] However, given intravenously at sufficiently high doses, tryptamine is still known to be able to produce weak and short-lived serotonergic psychedelic effects in humans. [15] [10] [1] [14]

The predicted log P of 5-MeT is 1.84 to 1.9. [16] [17]

See also

Related Research Articles

<span class="mw-page-title-main">Tryptamine</span> Metabolite of the amino acid tryptophan

Tryptamine is an indolamine metabolite of the essential amino acid tryptophan. The chemical structure is defined by an indole—a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon. 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.

<span class="mw-page-title-main">5-HT receptor</span> Class of transmembrane proteins

5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neurotransmission. The serotonin receptors are activated by the neurotransmitter serotonin, which acts as their natural ligand.

<span class="mw-page-title-main">5-MeO-AMT</span> Chemical compound

5-MeO-αMT, or 5-methoxy-α-methyltryptamine, also known as α,O-dimethylserotonin (Alpha-O), is a serotonergic psychedelic of the tryptamine family. It is a derivative of α-methyltryptamine (αMT) and an analogue of 5-MeO-DMT.

<span class="mw-page-title-main">Serotonin receptor agonist</span> Neurotransmission-modulating substance

A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin, a neurotransmitter and hormone and the endogenous ligand of the serotonin receptors.

<span class="mw-page-title-main">5-Methoxytryptamine</span> Chemical compound

5-Methoxytryptamine, also known as serotonin methyl ether or O-methylserotonin and as mexamine, is a tryptamine derivative closely related to the neurotransmitters serotonin and melatonin. It has been shown to occur naturally in the body in low levels, especially in the pineal gland. It is formed via O-methylation of serotonin or N-deacetylation of melatonin.

5-HT<sub>1D</sub> receptor Serotonin receptor which affects locomotion and anxiety in humans

5-hydroxytryptamine (serotonin) receptor 1D, also known as HTR1D, is a 5-HT receptor, but also denotes the human gene encoding it. 5-HT1D acts on the central nervous system, and affects locomotion and anxiety. It also induces vasoconstriction in the brain.

5-HT<sub>5A</sub> receptor Protein-coding gene in the species Homo sapiens

5-Hydroxytryptamine (serotonin) receptor 5A, also known as HTR5A, is a protein that in humans is encoded by the HTR5A gene. Agonists and antagonists for 5-HT receptors, as well as serotonin uptake inhibitors, present promnesic (memory-promoting) and/or anti-amnesic effects under different conditions, and 5-HT receptors are also associated with neural changes.

<span class="mw-page-title-main">5-Carboxamidotryptamine</span> Chemical compound

5-Carboxamidotryptamine (5-CT) is a tryptamine derivative closely related to the neurotransmitter serotonin.

Triptans are a family of tryptamine-based drugs used as abortive medication in the treatment of migraines and cluster headaches. They are selective 5-hydroxytryptamine/serotonin1B/1D (5-HT1B/1D) agonists. Migraine is a complex disease which affects about 15% of the population and can be highly disabling. Triptans have advantages over ergotamine and dihydroergotamine, such as selective pharmacology, well established safety record and evidence-based prescribing instructions. Triptans are therefore often preferred treatment in migraine.

α-Methylserotonin Chemical compound

α-Methylserotonin (αMS), also known as α-methyl-5-hydroxytryptamine (α-methyl-5-HT) or 5-hydroxy-α-methyltryptamine (5-HO-αMT), is a tryptamine derivative closely related to the neurotransmitter serotonin (5-HT). It acts as a non-selective serotonin receptor agonist and has been used extensively in scientific research to study the function of the serotonin system.

<span class="mw-page-title-main">2-Methyl-5-hydroxytryptamine</span> Chemical compound

2-Methyl-5-hydroxytryptamine (2-Methylserotonin, 2-Methyl-5-HT) is a tryptamine derivative closely related to the neurotransmitter serotonin which acts as a moderately selective full agonist at the 5-HT3 receptor.

<span class="mw-page-title-main">Serotonin releasing agent</span> Class of compounds

A serotonin releasing agent (SRA) is a type of drug that induces the release of serotonin into the neuronal synaptic cleft. A selective serotonin releasing agent (SSRA) is an SRA with less significant or no efficacy in producing neurotransmitter efflux at other types of monoamine neurons, including dopamine and norepinephrine neurons.

<span class="mw-page-title-main">Serotonin–dopamine releasing agent</span> Drug that releases serotonin and dopamine in the brain

A serotonin–dopamine releasing agent (SDRA) is a type of drug which induces the release of serotonin and dopamine in the body and/or brain.

<span class="mw-page-title-main">GR-127935</span> Drug

GR-127935 is a drug which acts as a selective antagonist at the serotonin receptors 5-HT1B and 5-HT1D. It has little effect when given by itself but blocks the antiaggressive effect of 5-HT1B agonists, and alters release of serotonin in the brain, as well as reducing drug-seeking behaviour in cocaine addicted rats.

<span class="mw-page-title-main">5-Benzyloxytryptamine</span> Chemical compound

5-Benzyloxytryptamine (5-BT), is a tryptamine derivative which acts as an agonist at the 5-HT1D, 5-HT2 and 5-HT6 serotonin receptors, and an antagonist of TRPM8.

<span class="mw-page-title-main">5-Ethyl-DMT</span> Chemical compound

5-Ethyl-N,N-dimethyltryptamine is a tryptamine derivative which acts as an agonist at the 5-HT1A and 5-HT1D serotonin receptors, with around 3x selectivity for 5-HT1D.

<span class="mw-page-title-main">5-(Nonyloxy)tryptamine</span> Chemical compound

5-(Nonyloxy)tryptamine (5-NOT) is a tryptamine derivative which acts as a selective agonist at the 5-HT1B receptor. Increasing the O-alkoxy chain length in this series gives generally increasing potency and selectivity for 5-HT1B, with highest activity found for the nonyloxy derivative, having a 5-HT1B binding affinity of 1.0 nM, and around 300-fold selectivity over the related 5-HT1A receptor.

<span class="mw-page-title-main">Substituted tryptamine</span> Class of indoles

Substituted tryptamines, or simply tryptamines, also known as serotonin analogues (i.e., 5-hydroxytryptamine analogues), are organic compounds which may be thought of as being derived from tryptamine itself. The molecular structures of all tryptamines contain an indole ring, joined to an amino (NH2) group via an ethyl (−CH2–CH2−) sidechain. In substituted tryptamines, the indole ring, sidechain, and/or amino group are modified by substituting another group for one of the hydrogen (H) atoms.

<span class="mw-page-title-main">5-Chloro-αMT</span> Chemical compound

5-Chloro-α-methyltryptamine (5-Chloro-αMT), also known as PAL-542, is a tryptamine derivative related to α-methyltryptamine (αMT) and one of only a few known serotonin–dopamine releasing agents (SDRAs). It is also a potent serotonin 5-HT2A receptor agonist and hence may be a serotonergic psychedelic. The drug has been investigated in animals as a potential treatment for cocaine dependence.

<span class="mw-page-title-main">Acetryptine</span> Drug

Acetryptine (INN), also known as 5-acetyltryptamine (5-AT), is a drug described as an antihypertensive agent which was never marketed. Structurally, acetryptine is a substituted tryptamine, and is closely related to other substituted tryptamines like serotonin (5-hydroxytryptamine). It was developed in the early 1960s. The binding of acetryptine to serotonin receptors does not seem to have been well-investigated, although it was assessed at the 5-HT1A and 5-HT1D receptors and found to bind to them with high affinity. The drug may also act as a monoamine oxidase inhibitor (MAOI); specifically, as an inhibitor of MAO-A.

References

  1. 1 2 3 4 5 6 7 Blough BE, Landavazo A, Partilla JS, Decker AM, Page KM, Baumann MH, et al. (October 2014). "Alpha-ethyltryptamines as dual dopamine-serotonin releasers". Bioorg Med Chem Lett. 24 (19): 4754–4758. doi:10.1016/j.bmcl.2014.07.062. PMC   4211607 . PMID   25193229.
  2. 1 2 3 4 Boess FG, Martin IL (1994). "Molecular biology of 5-HT receptors". Neuropharmacology. 33 (3–4): 275–317. doi:10.1016/0028-3908(94)90059-0. PMID   7984267.
  3. ↑ Soblosky JS, Dills C, DuMontier G, Jeng I (May 1987). "Evidence for 5-HT1A binding sites in chick embryo brain and discrimination by 5-methoxytryptamine". Biochem Int. 14 (5): 797–803. PMID   2970262.
  4. ↑ Cushing DJ, Baez M, Kursar JD, Schenck K, Cohen ML (1994). "Serotonin-induced contraction in canine coronary artery and saphenous vein: role of a 5-HT1D-like receptor". Life Sci. 54 (22): 1671–1680. doi:10.1016/0024-3205(94)00607-5. PMID   7909909.
  5. ↑ Uchiyama-Tsuyuki Y, Saitoh M, Muramatsu M (1996). "Identification and characterization of the 5-HT4 receptor in the intestinal tract and striatum of the guinea pig". Life Sci. 59 (25–26): 2129–2137. doi:10.1016/s0024-3205(96)00569-3. PMID   8950316.
  6. ↑ Watts SW, Cohen ML (January 1993). "Further evidence that the guinea pig tracheal contractile serotonergic receptor is a 5-hydroxytryptamine2 receptor: use of 5-methyltryptamine and dipropyl-5-carboxamidotryptamine". J Pharmacol Exp Ther. 264 (1): 271–275. PMID   8423530.
  7. ↑ Garro MA, López de Jesús M, Ruíz de Azúa I, Callado LF, Meana JJ, Sallés J (April 2001). "Regulation of phospholipase Cbeta activity by muscarinic acetylcholine and 5-HT(2) receptors in crude and synaptosomal membranes from human cerebral cortex". Neuropharmacology. 40 (5): 686–95. doi:10.1016/s0028-3908(00)00206-9. PMID   11311896.
  8. ↑ Bower KS, Price KL, Sturdee LE, Dayrell M, Dougherty DA, Lummis SC (February 2008). "5-Fluorotryptamine is a partial agonist at 5-HT3 receptors, and reveals that size and electronegativity at the 5 position of tryptamine are critical for efficient receptor function". Eur J Pharmacol. 580 (3): 291–297. doi:10.1016/j.ejphar.2007.11.014. PMC   2649378 . PMID   18082160.
  9. ↑ Jones RS (1982). "Tryptamine: a neuromodulator or neurotransmitter in mammalian brain?". Prog Neurobiol. 19 (1–2): 117–139. doi:10.1016/0301-0082(82)90023-5. PMID   6131482.
  10. 1 2 Shulgin A (1997). Tihkal: The Continuation. Transform Press. #53. T. ISBN   978-0-9630096-9-2 . Retrieved 17 August 2024. (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."
  11. ↑ Nichols DE (2012). "Structure–activity relationships of serotonin 5‐HT 2A agonists". Wiley Interdisciplinary Reviews: Membrane Transport and Signaling. 1 (5): 559–579. doi: 10.1002/wmts.42 . ISSN   2190-460X.
  12. ↑ Nichols DE (2018). "Chemistry and Structure-Activity Relationships of Psychedelics". Curr Top Behav Neurosci. 36: 1–43. doi:10.1007/7854_2017_475. PMID   28401524.
  13. ↑ Prozialeck WC, Vogel WH (February 1979). "MAO inhibition and the effects of centrally administered LSD, serotonin, and 5-methoxytryptamine on the conditioned avoidance response in rats". Psychopharmacology (Berl). 60 (3): 309–310. doi:10.1007/BF00426673. PMID   108709. In contrast, MAO inhibition greatly increased brain levels of 5-HT and 5-MT (Prozialeck and Vogel, 1978). For instance, clorgyline and deprenyl increased brain levels of 5-HT 8.5-fold and 4.4-fold and of 5-MT 20-fold and 5-fold, respectively.
  14. 1 2 Martin WR, Sloan JW (1970). "Effects of infused tryptamine in man". Psychopharmacologia. 18 (3): 231–237. doi:10.1007/BF00412669. PMID   4922520.
  15. ↑ Martin WR, Sloan JW (1977). "Pharmacology and Classification of LSD-like Hallucinogens". Drug Addiction II. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 305–368. doi:10.1007/978-3-642-66709-1_3. ISBN   978-3-642-66711-4. 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). [...]
  16. ↑ "5-Methyltryptamine". PubChem. Retrieved 15 January 2025.
  17. ↑ "5-methyltryptamine". ChemSpider. 10 June 2024. Retrieved 15 January 2025.


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