Chemistry:5-Methoxytryptamine

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5-Methoxytryptamine (5-MT, 5-MeO-T, or 5-OMe-T), also known as serotonin methyl ether or O-methylserotonin and as mexamine, is a tryptamine derivative closely related to the neurotransmitters serotonin and melatonin.[1] It has been shown to occur naturally in the pineal gland of the brain.[1][2] It is formed via O-methylation of serotonin or N-deacetylation of melatonin.[1][3][2]

5-MT is a highly potent and non-selective serotonin receptor agonist[4][5][6][7] and shows psychedelic-like effects in animals.[8][9][10][11] However, it is inactive in humans, at least orally, likely due to rapid metabolism by monoamine oxidase (MAO).[12][13][14] The levels and effects of 5-MT are dramatically potentiated by monoamine oxidase inhibitors (MAOIs) in animals.[15][16][17][18][19][20]

5-MT was first described in the scientific literature by at least 1925.[21][22][23]

Use and effects

5-MT is only briefly mentioned in Alexander Shulgin's TiHKAL (Tryptamines I Have Known and Loved) and its psychoactive effects are not described.[24][25][26] Nonetheless, 5-MT has been said by other sources to produce mild psychoactive effects in humans.[27] In addition, it has been reported to potentiate the effects of other drugs such as LSD and THC.[27] The drug is said to be orally inactive in humans.[12][13] It has been given to humans orally in clinical studies at doses of up to 8.5 mg/kg body weight (or ~600 mg for a 70-kg individual) without hallucinogenic effects described.[28][14][29][30][31][32][33]

Pharmacology

Pharmacodynamics

Actions

5-MT activities
Target Affinity (Ki, nM)
5-HT1A 3.2–9 (Ki)
1.1–535 (EC50)
66–135% (Emax)
5-HT1B 0.75–38
5-HT1D 1.7–34
5-HT1E 397–3,151
5-HT1F 1,166
5-HT2A 4.8–724 (Ki)
0.50–9.0 (EC50)
85–119% (Emax)
5-HT2B 0.51–16 (Ki)
0.7–1.6 (EC50)
99–103% (Emax)
5-HT2C 7.1–943 (Ki)
0.1–1.5 (EC50)
100–104% (Emax)
5-HT3 >10,000
5-HT4 27–2,443 (Ki)
437 (EC50) (pig)
107% (Emax) (pig)
5-HT5A 45.5
98 (unknown)
5-HT6 18–119
5-HT7 0.5–15
MT1 >10,000
MT2 >10,000
α2A 1,835
α2B >10,000
α2C 2,174
D2 >10,000
D3 >10,000
D4 1,422
H1, H3 >10,000
σ1, σ2 >10,000
KOR >10,000
SERT >10,000
4,000 (IC50)
2,169 (EC50)
NET >10,000 (IC50)
>10,000 (EC50)
DAT >10,000 (IC50)
11,031 (EC50)
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [4][5][6][7][34][35][36][37][38][39]

5-MT acts as an agonist of the serotonin 5-HT1, 5-HT2, 5-HT4, 5-HT6, and 5-HT7 receptors.[40][41][42][43][44][45][46][47] Conversely, it is completely devoid of activity at the serotonin 5-HT3 receptor.[48][49]

The drug is an extremely potent serotonin 5-HT2A receptor agonist in vitro, with an EC50 of 0.5 nM in one study.[6] This was more potent than any other tryptamine evaluated in a large series of compounds.[6][7] For comparison, 5-MeO-DMT had an EC50 of 3.87 nM (7.7-fold lower) and dimethyltryptamine (DMT) had an EC50 of 38.3 nM (76-fold lower).[7]

5-MT has been said in the past to be 25- and 400-fold selective for the serotonin 5-HT2B receptor over the serotonin 5-HT2A and 5-HT2C receptors, respectively.[50] Conversely however, a more modern study found EC50 values for activation of Gαq signaling of 2.6 nM at the serotonin 5-HT2A receptor, 0.7 nM at the serotonin 5-HT2B receptor, and 0.1 nM at the serotonin 5-HT2C receptor, indicating preference for the serotonin 5-HT2C receptor rather than for the serotonin 5-HT2B receptor.[38]

The drug has been found to show substantially higher affinity for the serotonin 5-HT1A receptor than tryptamine or DMT (Ki = 6.1 nM, 125 nM, and 245 nM, respectively; 20- to 40-fold higher affinity).[51] On the other hand, it shows slightly lower affinity for this receptor than serotonin but a little more than twice the affinity of 5-MeO-DMT (Ki = 3.2 nM, 1.7 nM, and 7.8 nM, respectively).[52]

5-MT, in contrast to the closely related melatonin, has no affinity for the melatonin receptors.[53][54] Conversely, in Tango assay at a concentration of 10 μM, it displayed agonist-like activity at the melatonin MT1 receptor.[38] The drug may also be converted into melatonin in the body, and hence may indirectly act as a melatonin receptor agonist.[1][3]

5-MT shows dramatically reduced activity as a monoamine releasing agent compared to tryptamine and serotonin.[6]

Effects

Both tryptamine and 5-MT failed to substitute for 5-MeO-DMT in rodent drug discrimination tests.[8][55][9] Instead, only behavioral disruption occurred, which it was theorized might be a peripherally mediated effect.[8][55][9]

On the other hand, 5-MT dose-dependently induces the head-twitch response (HTR), a behavioral proxy of psychedelic effects, in rodents, and this effect is reversed by serotonin 5-HT2A receptor antagonists.[11][19][20][56][57][58][59] As such, it may theoretically be hallucinogenic in humans.[60] However, in a couple of other more recent studies, 5-MT failed to produce the HTR, instead inducing only serotonin 5-HT1A receptor-mediated hypothermia and hypolocomotion.[38][61][62] In one of these studies, the ED50 of 5-MT in producing the HTR was greater than 30 mg/kg, whereas the ED50 of 5-MeO-DMT was 0.33 mg/kg, an at least 91-fold difference in dose.[38] Conversely, the drug was 2.8-fold more potent than 5-MeO-DMT in producing hypolocomotion and was only slightly less potent than 5-MeO-DMT in producing hypothermia.[38] Co-administration of the serotonin 5-HT1A receptor antagonist WAY-100635 did not unmask an HTR with 5-MT, similarly to the case of 5-MeO-NMT but in contrast to the case of 5-MeO-NET.[38] It was hypothesized that reduced blood–brain barrier permeability with drugs like 5-MT might be involved in these findings.[38]

Besides the preceding effects, 5-MT produces a "hyperactivity syndrome" in rodents.[1][15][63] It produces various other effects in animals as well.[1] 5-MT has been reported to produce weak psychedelic-like behavioral effects in monkeys at relatively high doses of 10 to 20 mg/kg.[8][9][10] The drug has also been studied as a possible LSD antagonist in rodents.[14][64]

Pharmacokinetics

Absorption

5-MT is said to be orally inactive in humans presumably due to rapid metabolism by monoamine oxidase (MAO).[12][13]

Distribution

5-MT is able to cross the blood–brain barrier and enter the central nervous system with peripheral administration in animals.[15] However, it has also been reported that 5-MT shows strong peripheral selectivity in animals comparable to serotonin and bufotenin and that its capacity to exert central effects is limited.[8][9][65][66]

Metabolism

5-MT is metabolized by deamination by monoamine oxidase (MAO), specifically monoamine oxidase A (MAO-A) and to a much lesser extent by monoamine oxidase B (MAO-B).[16][17][18][67] Metabolites of 5-MT include 5-methoxyindole-3-acetic acid (5-MIAA) and 5-methoxytryptophol.[1][18] It may also be metabolized into melatonin.[1][3]

Brain levels of 5-MT following central administration of 5-MT in rats were potentiated by 20-fold by the MAO-A inhibitor clorgyline and by 5.5-fold by the MAO-B inhibitor selegiline.[17][16] Similarly, levels of serotonin and phenethylamine were also greatly elevated by these drugs.[16][17] In accordance with the potentiation of brain levels of 5-MT by MAOIs, the behavioral effects of centrally administered 5-MT in rats, for instance in the conditioned avoidance response test, are markedly enhanced by MAOIs, including by the dual MAO-A and MAO-B inhibitor iproniazid as well as by clorgyline and selegiline.[17] The non-selective MAO-A and MAO-B inhibitor tranylcypromine has also been frequently used to potentiate the effects of 5-MT in animal studies.[15][57][59][19][20] Similarly to the exogenous rat findings, pineal gland levels of endogenous 5-MT are dramatically elevated by the MAO-A inhibitor clorgyline and by the dual MAO-A and MAO-B inhibitor pargyline in hamsters, and plasma levels of exogenous 5-MT are greatly elevated by these MAOIs as well.[18] Conversely, selegiline was ineffective in elevating brain or plasma 5-MT levels in hamsters.[18]

Chemistry

5-MT, also known as 5-methoxytryptamine or as 5-hydroxytrypamine O-methyl ether, is a substituted tryptamine and a derivative of serotonin (5-hydroxytryptamine) and precursor of melatonin (N-acetyl-5-methoxytryptamine).[68]

Synthesis

The chemical synthesis of 5-MT has been described.[21]

Properties

The predicted log P of 5-MT is 0.5 to 1.41.[68][69][70]

Analogues and derivatives

5-MT is closely related to other 5-methoxylated tryptamines such as 5-MeO-NMT, 5-MeO-DMT, 5-MeO-DPT, 5-MeO-DiPT, 5-MeO-MiPT, 5-MeO-DALT, and 5-MeO-AMT.[24] 5-MeO-AMT is orally active in humans, in contrast to 5-MT, and could be thought of as a sort of orally active form of 5-MT.[13][24] Some other notable analogues of 5-MT include tryptamine, 2-methyl-5-hydroxytryptamine, 5-phenoxytryptamine, 5-benzyloxytryptamine, 5-carboxamidotryptamine, 5-methyltryptamine, 5-(nonyloxy)tryptamine, α-methyl-5-hydroxytryptamine, acetryptine (5-acetyltryptamine), and isamide (N-chloroacetyl-5-methoxytryptamine), among others. Cyclized tryptamine derivatives and analogues of 5-MT include RU-28253 (5-MeO-THPI) and RU-24969, among others.[51]

α,α,β,β-Tetradeutero-5-methoxytryptamine (5-MT-d4), a deuterated isotopologue of 5-methoxytryptamine, has been described.[71][72][73]

Natural occurrence

Biosynthesis

5-MT can be formed by O-methylation of serotonin mediated by hydroxyindole O-methyltransferase (HIOMT) or by N-deacetylation of melatonin.[1][3] It is also a precursor of 5-MeO-DMT in some species.[1]

History

5-MT was first described in the scientific literature by at least 1925.[21][22][23] Subsequently, it was studied in the 1950s following the discovery of serotonin's chemical structure in the late 1940s and early 1950s.[74][75][76] The drug was extensively studied under the name mexamine (or meksamina) as a radioprotective agent by the Soviet Union from the 1960s and thereafter.[77][78][24][79] It briefly described by Alexander Shulgin in his book TiHKAL (Tryptamines I Have Known and Loved) in 1997.[24] 5-MT was encountered online as a reported designer drug by 2023.[27]

Society and culture

Canada

5-MT is not a controlled substance in Canada as of 2025.[80]

United states

5-MT is not an explicitly controlled substance in the United States.[81] However, it could be considered a controlled substance under the Federal Analogue Act if intended for human consumption.

See also

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 "Is 5-methoxytryptamine a pineal hormone?". Psychoneuroendocrinology 8 (1): 61–73. 1983. doi:10.1016/0306-4530(83)90041-0. PMID 6136058. 
  2. ↑ 2.0 2.1 "Day-night rhythm of 5-methoxytryptamine biosynthesis in the pineal gland of the golden hamster (Mesocricetus auratus).". The Journal of Endocrinology 118 (3): 389–397. 1988. doi:10.1677/joe.0.1180389. PMID 2460575. 
  3. ↑ 3.0 3.1 3.2 3.3 "On the significance of an alternate pathway of melatonin synthesis via 5-methoxytryptamine: comparisons across species". Journal of Pineal Research 61 (1): 27–40. August 2016. doi:10.1111/jpi.12336. PMID 27112772. 
  4. ↑ 4.0 4.1 "PDSP Database" (in zu). https://pdsp.unc.edu/databases/pdsp.php?testFreeRadio=testFreeRadio&testLigand=5-methoxytryptamine&kiAllRadio=all&doQuery=Submit+Query. 
  5. ↑ 5.0 5.1 "BindingDB BDBM82087 2-(5-methoxy-1H-indol-3-yl)ethanamine::5-MT::5-Methoxytryptamine hydrochloride::CAS_66-83-1::tryptamine, 5-Methoxy". https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=82087. 
  6. ↑ 6.0 6.1 6.2 6.3 6.4 "Alpha-ethyltryptamines as dual dopamine-serotonin releasers". Bioorganic & Medicinal Chemistry Letters 24 (19): 4754–4758. October 2014. doi:10.1016/j.bmcl.2014.07.062. PMID 25193229. 
  7. ↑ 7.0 7.1 7.2 7.3 "Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes". Psychopharmacology (Berl) 231 (21): 4135–4144. October 2014. doi:10.1007/s00213-014-3557-7. PMID 24800892. 
  8. ↑ 8.0 8.1 8.2 8.3 8.4 "Medicinal Chemistry and Structure-Activity Relationships of Hallucinogens". Hallucinogens: Neurochemical, Behavioral, and Clinical Perspectives. New York: Raven Press. 1984. pp. 95–142. ISBN 978-0-89004-990-7. OCLC 10324237. https://bitnest.netfirms.com/external/Books/HallucinogensNBCP95. "5-Methoxytryptamine has been shown to be more potent than tryptamine [...] in displacing 3H-LSD from rat brain homogenates (95). However, none of these compounds has shown any significant behavioral activity in animal models. [...] Martin and co-workers (142,143) have found that, in animals, tryptamine produced many of the physiologic effects characteristic of LSD; however, it does not appear to elicit behavioral effects similar to those of LSD. At relatively high doses, 5-methoxytryptamine (24) does produce some behavioral effects in rats (66,242) and in nonhuman primates (101). Vogel (242) has suggested that the disruptive effects of 5-methoxytryptamine might be due to the peripheral actions of this agent. Tryptamine had no effect on acquisition of avoidance behavior, whereas 5-methoxytryptamine slightly decreased such behavior (240). Both tryptamine and 5-methoxytryptamine produced discriminative effects in rats that were dissimilar to those of the hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-OMeDMT; 59). Administration of either 22 or 24 to rats trained to discriminate 5-OMeDMT from saline did not result in stimulus generalization (84). [...] Tryptamines that are unsubstituted on the terminal amine are good substrates for oxidative deamination by MAO. Furthermore, it has been demonstrated that tryptamine and 5-methoxytryptamine cross the blood-brain barrier with great difficulty; administration of 50 mg/kg 5-methoxytryptamine to rats results in a low brain/plasma ratio when measured 15 min post-administration (242)." 
  9. ↑ 9.0 9.1 9.2 9.3 9.4 "Indolealkylamine and phenalkylamine hallucinogens: a brief overview". Neuroscience and Biobehavioral Reviews 6 (4): 489–497. 1982. doi:10.1016/0149-7634(82)90030-6. PMID 6757811. "Martin and Sloan have reported that tryptamine (1 a), itself, produces little central effect in man [43]. Its 5-methoxy derivative (i.e., 5-methoxytryptamine, 5-OMeT; 1b) produces some behavioral effects in rats [19] and, at high doses, in non-human primates [31]. On the other hand, in tests of discriminative stimulus (DS) control, generalization does not occur when either tryptamine (1a) or 5-OMeT (1b) is administered to groups of rats trained to discriminate the hallucinogenic agent 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT) from saline [23]. The finding of little or no activity for tryptamine derivatives which are unsubstituted on the a-carbon or terminal amine may be a consequence of rapid metabolism in vivo by, for example, oxidative deamination. [...] Furthermore, evidence suggests that certain tryptamines penetrate the blood-brain barrier only with great difficulty. [...] They suggest, based on the amount of drug that actually gets into the brain, that 5-OMeT (1b) is actually more potent than either DMT (3a) or 5-OMe DMT (3e) and that, in fact, it may be equipotent with LSD; [...] Administration of larger doses of 1b, in order to achieve greater brain levels, manifests itself in disruption of behavior, which may be a peripherally-mediated event [76].". 
  10. ↑ 10.0 10.1 "The acute and chronic effect of 5-methoxytryptamine on selected members of a primate social colony". Biological Psychiatry 15 (6): 829–839. December 1980. PMID 6936054. 
  11. ↑ 11.0 11.1 "5-Methoxytryptamine-induced head twitches in rats". Polish Journal of Pharmacology and Pharmacy 29 (3): 253–261. 1977. PMID 267911. 
  12. ↑ 12.0 12.1 12.2 "Structure–activity relationships of serotonin 5-HT 2A agonists". Wiley Interdisciplinary Reviews: Membrane Transport and Signaling 1 (5): 559–579. 2012. doi:10.1002/wmts.42. ISSN 2190-460X. 
  13. ↑ 13.0 13.1 13.2 13.3 "Chemistry and Structure–Activity Relationships of Psychedelics". Behavioral Neurobiology of Psychedelic Drugs. Current Topics in Behavioral Neurosciences. 36. 2018. pp. 1–43. doi:10.1007/7854_2017_475. ISBN 978-3-662-55878-2. 
  14. ↑ 14.0 14.1 14.2 "K toksikologii meksamina" (in Russian). Farmakologiia i Toksikologiia 31 (6): 731–733. 1968. PMID 5753235. https://books.google.com/books?id=L2oFAQAAIAAJ&q=on+the+toxicology+of+mexamine. "Mexamine tolerance was measured following enteral administration of 7.5 mg/kg in man after an initial dose of 1 mg/kg had been taken 30 minutes prior. The complex set of investigations included study es of the mexamine effects on the bioelectric activity of the brain, arterial pressure level, pulse rate and body temperature of the persons under examination. Enteral administration to humans of mexamine in a dose of 7.5 mg/kg in the experiment does not produce any substantial side-effects and may be recommended for clinical use. [...]". 
  15. ↑ 15.0 15.1 15.2 15.3 "The concentration of 5-methoxytryptamine in rat brain and its effects on behaviour following its peripheral injection". Neuropharmacology 14 (8): 601–606. August 1975. doi:10.1016/0028-3908(75)90127-6. PMID 126386. 
  16. ↑ 16.0 16.1 16.2 16.3 "Deamination of 5-methoxytryptamine, serotonin and phenylethylamine by rat MAO in vitro and in vivo". Life Sciences 22 (7): 561–569. February 1978. doi:10.1016/0024-3205(78)90334-x. PMID 272480. 
  17. ↑ 17.0 17.1 17.2 17.3 17.4 "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. February 1979. 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.". 
  18. ↑ 18.0 18.1 18.2 18.3 18.4 "5-Methoxytryptamine is metabolized by monoamine oxidase A in the pineal gland and plasma of golden hamsters". Neuroscience Letters 123 (2): 172–174. February 1991. doi:10.1016/0304-3940(91)90923-h. PMID 2027530. 
  19. ↑ 19.0 19.1 19.2 "Head twitches produced by serotonergic drugs and opiates after lesion of the mesostriatal serotonergic system of the rat". Polish Journal of Pharmacology and Pharmacy 31 (4): 413–423. 1979. PMID 316525. 
  20. ↑ 20.0 20.1 20.2 "Effects of histamine and H1 and H2-receptor antagonists on wet-dog-shake episodes in rats induced with tranylcypromine and 5-methoxytryptamine". Acta Physiologica Polonica 35 (3): 225–230. 1984. PMID 6152672. 
  21. ↑ 21.0 21.1 21.2 "Trout’s Notes FS-X7". https://isomerdesign.com/bitnest/external/SST/116-118. 
  22. ↑ 22.0 22.1 "Synthetische Versuche in der Indol‐Gruppe, VI.: Eine neue Synthese von β‐Indolyl‐alkylaminen". Berichte der deutschen chemischen Gesellschaft (A and B Series) 58 (9): 2042–2046. 14 October 1925. doi:10.1002/cber.19250580917. ISSN 0365-9488. 
  23. ↑ 23.0 23.1 Blanchard, W. M. (1935). Increasing Recognition of the Importance of Tryptophane as a Prototype in Phytochemical Processes. In Proceedings of the Indiana Academy of Science (Vol. 45, pp. 124-130). "The methoxyindoles were prepared by the method of Kenneth Guy Blaikie and William H. Perkin, Jr. (32). From these the methoxytryptamines were prepared by the method of Akabori and Suzuki (33). Methylation of the 6-methoxytryptamine with methyl iodide and thallium exthoxide gave a compound which seemed to be identical with that obtained from bufotenine, but the mixed melting point proved otherwise. On methylating the 5-methoxytryptamine they obtained a compound which was shown to be identical with that obtained from natural bufotenine."
  24. ↑ 24.0 24.1 24.2 24.3 24.4 TiHKAL: The Continuation. Transform Press. 1997. ISBN 978-0-9630096-9-2. https://www.thevespiary.org/rhodium/Rhodium/hive/hiveboard/picproxie_docs/000532880-Alexander_Shulgin_and_Ann_Shulgin_-_TiHKAL.pdf. Retrieved 2 November 2024. "One of its most broadly studied properties is that of protecting an experimental animal against the damage of being exposed to radiation. It was unexpectedly observed that our essential and favorite neurotransmitter serotonin was every bit as effective as a radioprotective agent. In efforts to make this natural compound more accessible to the damaged animal, it was studied as the unacetylated O-methyl ether. This simple compound, 5-methoxytryptamine (5-MeO-T, or Mexamine) has been mentioned under the recipe for 5-MeO-DMT in its possible effects in potentiating CNS-active drugs. But here it deserves to be highlighted for its protection against radiation. Two structural modification directions of 5-methoxytryptamine have been thoroughly explored. [...] A A 5-MeO-T anti-radiation, not a psychedelic ? [...] Removal of both methyl groups from the nitrogen gives 5-methoxytryptamine (5-MeO-T) which has been explored most extensively by Soviet researchers as a treatment for exposure to radiation; this aspect of its action is discussed and expanded upon in the commentary under Melatonin. It is also known by the trade name Mexamine and has been looked at as a potentiator of centrally active drugs." 
  25. ↑ "5-MeO-T - PiHKAL·info". 11 November 2024. https://isomerdesign.com/pihkal/explore/5143. 
  26. ↑ "Psychoactive natural products: overview of recent developments". Ann Ist Super Sanita 50 (1): 12–27. 2014. doi:10.4415/ANN_14_01_04. PMID 24695249. "A related substance worth mentioning here is 5-methoxytryptamine, mexamine or 5-MeO-T. This endogenous trace amine is a serotonin receptor agonist and an enigmatic minor metabolite of the multifunctional neurohormone melatonin [96]. It has antioxidant and radioprotective effects in various biological systems but there is no information on its psychoactivity.". 
  27. ↑ 27.0 27.1 27.2 AIPSIN. "5-MeO-T (5-methoxytryptamine)" (in ru). https://aipsin.com/newsubstance/1200/. 
  28. ↑ United States John E. Fogarty International Center for Advanced Study in the Health Sciences (1974). Soviet Research in Pharmacology and Toxicology. p. 38. https://books.google.com/books?id=WjcCSYMkXQcC&pg=PA38. Retrieved 11 June 2026. "Strelkov and Khasabova (570) studied the toxicological properties of mexamine, an analog of serotonin. Mexamine tolerance was measured following enteral administration of 7.5 mg/kg in man after an initial dose of 1 mg/kg had been taken 30 minutes prior. Other measurements made included the effect of the drug on the bioelectric potential of the brain, arterial pressure, pulse rate and body temperature of human subjects. It was concluded that enteral administration of 7.5 mg/kg did not produce any substantial side-effects and that mexamine could be recommended for clinical use." 
  29. ↑ "Cancer as the main aging factor for humans: the fundamental role of 5-methoxy-tryptamine in reversal of cancer-induced aging processes in metabolic and immune reactions by non-melatonin pineal hormones". Current Aging Science 5 (3): 231–235. December 2012. doi:10.2174/1874609811205030010. PMID 23451999. 
  30. ↑ "Biochemotherapy with immunomodulating pineal hormones other than melatonin: 5-methoxytryptamine as a new oncostatic pineal agent". Pathologie-Biologie (Paris) 55 (3–4): 198–200. 2007. doi:10.1016/j.patbio.2006.12.008. PMID 17451889. 
  31. ↑ "Reduction of cisplatin-induced anemia by the pineal indole 5-methoxytryptamine in metastatic lung cancer patients". Neuro Endocrinology Letters 24 (1–2): 83–85. 2003. PMID 12743539. 
  32. ↑ "Thrombopoietic properties of 5-methoxytryptamine plus melatonin versus melatonin alone in the treatment of cancer-related thrombocytopenia". Journal of Pineal Research 30 (2): 123–126. March 2001. doi:10.1034/j.1600-079x.2001.300208.x. PMID 11270479. 
  33. ↑ "Modulation of anticancer cytokines IL-2 and IL-12 by melatonin and the other pineal indoles 5-methoxytryptamine and 5-methoxytryptophol in the treatment of human neoplasms". Annals of the New York Academy of Sciences 917: 560–567. 2000. doi:10.1111/j.1749-6632.2000.tb05421.x. PMID 11268384. 
  34. ↑ "Medicinal chemistry of 5-HT5A receptor ligands: a receptor subtype with unique therapeutical potential". Current Topics in Medicinal Chemistry 10 (5): 554–578. 2010. doi:10.2174/156802610791111588. PMID 20166946. 
  35. ↑ "5-HT2A, 5-HT2B and 5-HT2C receptor ligands". Pharmacochemistry Library. 27. Elsevier. 1997. pp. 161–197. doi:10.1016/s0165-7208(97)80013-x. ISBN 978-0-444-82041-9. 
  36. ↑ "Agonist high and low affinity state ratios predict drug intrinsic activity and a revised ternary complex mechanism at serotonin 5-HT(2A) and 5-HT(2C) receptors". Synapse (New York, N.Y.) 35 (2): 144–150. February 2000. doi:10.1002/(SICI)1098-2396(200002)35:2<144::AID-SYN7>3.0.CO;2-K. PMID 10611640. 
  37. ↑ "Characterization of the 5-HT4 receptor mediating tachycardia in piglet isolated right atrium". British Journal of Pharmacology 110 (3): 1023–1030. November 1993. doi:10.1111/j.1476-5381.1993.tb13916.x. PMID 8298790. 
  38. ↑ 38.0 38.1 38.2 38.3 38.4 38.5 38.6 38.7 "Serotonin 1A Receptors Modulate Serotonin 2A Receptor-Mediated Behavioral Effects of 5-Methoxy-N,N-dimethyltryptamine Analogs in Mice". ACS Chemical Neuroscience 15 (24): 4458–4477. December 2024. doi:10.1021/acschemneuro.4c00513. PMID 39636099. 
  39. ↑ "Low-basicity 5-HT7 Receptor Agonists Synthesized Using the van Leusen Multicomponent Protocol". Scientific Reports 7 (1). May 2017. doi:10.1038/s41598-017-00822-4. PMID 28473721. 
  40. ↑ "Serotonin-1A receptor activation in hippocampal CA1 neurons by 8-hydroxy-2-(di-n-propylamino)tetralin, 5-methoxytryptamine and 5-hydroxytryptamine.". Neuroscience Letters 86 (1): 72–76. 1988. doi:10.1016/0304-3940(88)90185-1. PMID 2966313. 
  41. ↑ "Hyperglycemia induced by the 5-HT receptor agonist, 5-methoxytryptamine, in rats: involvement of the peripheral 5-HT2A receptor.". European Journal of Pharmacology 323 (2–3): 235–240. 1997. doi:10.1016/S0014-2999(97)00029-0. PMID 9128844. 
  42. ↑ "Characterization of the contractile response induced by 5-methoxytryptamine in rat stomach fundus strips.". European Journal of Pharmacology 318 (2–3): 403–409. 1996. doi:10.1016/S0014-2999(96)00777-7. PMID 9016931. 
  43. ↑ "5-Methoxytryptamine and 2-methyl-5-hydroxytryptamine-induced desensitization as a discriminative tool for the 5-HT3 and putative 5-HT4 receptors in guinea pig ileum.". Naunyn-Schmiedeberg's Archives of Pharmacology 342 (1): 9–16. 1990. doi:10.1007/bf00178965. PMID 2402303. 
  44. ↑ "Functional and radioligand binding characterization of rat 5-HT6 receptors stably expressed in HEK293 cells.". Neuropharmacology 36 (4–5): 713–720. 1997. doi:10.1016/S0028-3908(97)00019-1. PMID 9225298. 
  45. ↑ "[3H-Mesulergine labels 5-HT7 sites in rat brain and guinea-pig ileum but not rat jejunum."]. British Journal of Pharmacology 126 (1): 179–188. 1999. doi:10.1038/sj.bjp.0702293. PMID 10051134. 
  46. ↑ "Serotonin Receptor Subtypes and Ligands". American College of Neurophyscopharmacology. 2000-01-01. http://www.acnp.org/g4/GN401000039/Ch039.html. 
  47. ↑ "Central serotonin receptors as targets for drug research". Journal of Medicinal Chemistry 30 (1): 1–12. January 1987. doi:10.1021/jm00384a001. PMID 3543362. "Table II. Affinities of Selected Phenalkylamines for 5-HT1 and 5-HT2 Binding Sites". 
  48. ↑ "5-HT3 receptors". Pharmacochemistry Library. 27. Elsevier. 1997. p. 221–258. doi:10.1016/s0165-7208(97)80016-5. ISBN 978-0-444-82041-9. https://linkinghub.elsevier.com/retrieve/pii/S0165720897800165. Retrieved 13 June 2026. 
  49. ↑ Fozard, John R. (1990). "Agonists and antagonists of 5-HT3 receptors". Cardiovascular Pharmacology of 5-Hydroxytryptamine. Dordrecht: Springer Netherlands. p. 101–115. doi:10.1007/978-94-009-0479-8_8. ISBN 978-94-010-6701-0. http://link.springer.com/10.1007/978-94-009-0479-8_8. Retrieved 13 June 2026. 
  50. ↑ Encyclopedia of Signaling Molecules. Cham: Springer International Publishing. 2018. doi:10.1007/978-3-319-67199-4. ISBN 978-3-319-67198-7. "1-Structure and properties of 5-HT2B receptors: 1.1-Selective agonists: [...] - 5-Methoxytryptamine is also 25- and 400-fold selective over the 5-HT2A and 5-HT2C receptor sites, respectively." 
  51. ↑ 51.0 51.1 "Relative selectivity of some conformationally constrained tryptamine analogs at 5-HT1, 5-HT1A and 5-HT2 recognition sites". Life Sci 41 (16): 1961–1969. October 1987. doi:10.1016/0024-3205(87)90749-1. PMID 3657392. 
  52. ↑ "N,N-di-n-propylserotonin: binding at serotonin binding sites and a comparison with 8-hydroxy-2-(di-n-propylamino)tetralin". J Med Chem 31 (4): 867–870. April 1988. doi:10.1021/jm00399a031. PMID 2965244. 
  53. ↑ "Recent progress in the development of agonists and antagonists for melatonin receptors". Current Medicinal Chemistry 19 (21): 3532–3549. 2012. doi:10.2174/092986712801323153. PMID 22680635. 
  54. ↑ "Development of Agonists and Antagonists for Melatonin Receptors". Melatonin and Melatonergic Drugs in Clinical Practice. New Delhi: Springer India. 2014. pp. 97–116. doi:10.1007/978-81-322-0825-9_7. ISBN 978-81-322-0824-2. 
  55. ↑ 55.0 55.1 "Indolealkylamine and phenalkylamine hallucinogens. Effect of alpha-methyl and N-methyl substituents on behavioral activity". Biochem Pharmacol 32 (7): 1267–1273. April 1983. doi:10.1016/0006-2952(83)90281-2. PMID 6573879. 
  56. ↑ "Effects of reserpine, para-chlorophenylalanine, 5,6-dihydroxytryptamine and fludiazepam on the head twitches induced by 5-hydroxytryptamine or 5-methoxytryptamine in mice". The Journal of Pharmacy and Pharmacology 30 (4): 254–256. April 1978. doi:10.1111/j.2042-7158.1978.tb13219.x. PMID 24719. 
  57. ↑ 57.0 57.1 "On the central antiserotonin activity of benzoctamine and opipramol". Polish Journal of Pharmacology and Pharmacy 30 (6): 781–790. 1978. PMID 582625. 
  58. ↑ "On the central antiserotonin action of trazodone". Polish Journal of Pharmacology and Pharmacy 31 (1): 25–33. 1979. PMID 482164. 
  59. ↑ 59.0 59.1 "The central action of pizotifen". Psychopharmacology (Berl) 62 (3): 295–300. April 1979. doi:10.1007/BF00431961. PMID 111296. 
  60. ↑ "Preferential action of 5-methoxytryptamine and 5-methoxydimethyltryptamine on presynaptic serotonin receptors: A comparative iontophoretic study with LSD and serotonin". Neuropharmacology 16 (12): 811–818. 1977. doi:10.1016/0028-3908(77)90142-3. 
  61. ↑ "A cane toad (Rhinella marina) N-methyltransferase converts primary indolethylamines to tertiary psychedelic amines". The Journal of Biological Chemistry 299 (10). October 2023. doi:10.1016/j.jbc.2023.105231. PMID 37690691. 
  62. ↑ Bioproduction platform using a novel cane toad (Rhinella marina) N-methyltransferase for psychedelic-inspired drug discovery, 10 March 2023, doi:10.21203/rs.3.rs-2667175/v1, https://www.researchsquare.com/article/rs-2667175/latest.pdf, retrieved 17 March 2025 
  63. ↑ "5-Methoxytryptamine: stimulation of 5-HT receptors mediating the rat hyperactivity syndrome and blood platelet aggregation". Advances in Biochemical Psychopharmacology 15: 127–140. 1976. PMID 15408. 
  64. ↑ "Vliianie meksamina na tsentral'nye éffekty diétilamida lizerginovoĭ kisloty" (in Russian). Farmakologiia i Toksikologiia 29 (6): 662–665. 1966. PMID 6000361. https://books.google.com/books?id=1BI88hn0iMQC&pg=PA39. "A study to test the possible antagonistic action of mexamine (5-metoxytryptamine, a preparation surmounting the hemato-encephalic barrier and capable of affecting the level of serotonin in the brain) on LSD, whose psychotomimetic properties are hypothesized to be connected with shifts in the volume of serotonin. [...] Dosages of LSD temporarily disrupt conditioned-reflex reactions: counterdosages of mexamine substantially accelerate normalization of previously elaborated conditioned-reflex behavior in mice and dogs subjected to the disorganizing action of LSD.". 
  65. ↑ "Structure-activity-relationships of certain hallucinogenic substances based on brain levels". Life Sci 20 (10): 1629–1635. May 1977. doi:10.1016/0024-3205(77)90335-6. PMID 69244. "A comparison based on brain levels (SAR II) leads to very different conclusions (43-47). The most potent compound is actually 5-methoxytryptamine ; brain levels are very low because the substance crosses the BBB only with great difficulty (46). Tryptamine alone is inactive because it is probably too rapidly metabolized (48); however, tryptamine after MAO-inhibition shows behavioral activity (43) and is close to 5-methoxytryptamine in potency. 5-Hydroxydimethyltryptamine [(bufotenine)] also is rather potent since the compound has difficulty crossing the BBB and only small amounts reach the CNS (45).". 
  66. ↑ "Physiological disposition of 5-methoxytryptamine and the rope climbing performance of rats". Psychopharmacologia 15 (2): 88–95. 1969. doi:10.1007/BF00407040. PMID 5351124. "The compound crosses the blood-brain barrier but to an extremely small extent; the concentration of 5-MT (after injection of 50 mg/kg) after 15 min is only 0.3 μg/g and the brain to plasma ratio is approximately 0.12. Similar values were obtained for the brain to blood ratio of serotonin (BULAT and SUPEK, 1968) and bufotenine (SANDERS and BUSH, 1967). The O-methyl derivative of bufotenine [(5-MeO-DMT)] crossed the blood-brain barrier rapidly (brain to blood ratio was 2) which indicates that both a free hydroxyl- and amino group impair passage of serotonin into the CNS. [...] After administration of 5-MT normal behavior of the animals is altered and they appear sedated. However, careful observations of the animals and the data presented make it unlikely that this effect is of central origin. First, the amounts of 5-MT found in the brain are extremely small. (Behavioral changes start at 0.05 µg/g and this value is probably smaller since some blood has remained in the brains after death.) Second, no marked changes in the cortical activity of the brain were noticed after 5-MT injection, [...] Third, 5-MT has marked peripheral actions. For instance, hypotension and hind leg paralysis could easily make an animal appear "sedated" and could readily interfere with behavioral tests in which unimpaired use of the hind legs is required. Thus, it is felt that behavioral changes in rats such as "sedation" or the altered conditioned escape response (GESSNER et al., 1961) and the impaired rope climbing performance observed after IP injections of 5-MT are mainly due to the peripheral and little, if any, to the central action of this compound.". 
  67. ↑ "Potentiation by deprenyl of the autoreceptor-mediated inhibition of [3H]-5-hydroxytryptamine release by 5-methoxytryptamine". Naunyn-Schmiedeberg's Archives of Pharmacology 333 (3): 330–333. July 1986. doi:10.1007/BF00512949. PMID 3093900. 
  68. ↑ 68.0 68.1 PubChem. "5-Methoxytryptamine". https://pubchem.ncbi.nlm.nih.gov/compound/1833. 
  69. ↑ "Metabolite 5-Methoxytryptamine". https://go.drugbank.com/metabolites/DBMET01359. 
  70. ↑ "5-Methoxytryptamine". 10 June 2024. https://www.chemspider.com/Chemical-Structure.1767.html. 
  71. ↑ "Analysis of 5-methoxytryptamine in brain by gas chromatography mass spectrometry". Biomedical Mass Spectrometry 6 (1): 19–22. January 1979. doi:10.1002/bms.1200060105. PMID 284809. 
  72. ↑ "An investigation of demethylation in the metabolism of methoxytryptamine and methoxytryptophol". Journal of Pineal Research 2 (1): 87–94. 1985. doi:10.1111/j.1600-079x.1985.tb00630.x. PMID 2420959. 
  73. ↑ PubChem. "5-METHOXYTRYPTAMINE-alpha,alpha,beta,beta-D4". https://pubchem.ncbi.nlm.nih.gov/compound/12273662. 
  74. ↑ "Pharmacology of Indolealkylamines". Pharmacological Reviews 6 (4): 425–487. December 1954. doi:10.1016/S0031-6997(25)07372-7. PMID 13236482. 
  75. ↑ "Pharmacological actions of synthetic 5-hydroxytryptamine (serotonin, thrombocytin)". Nature 169 (4306): 801–802. May 1952. doi:10.1038/169801a0. PMID 14941052. 
  76. ↑ "Observations on alleged serotonin- (enteramine)-like nature of cerebral pressor substance of Taylor, Page, and Corcoran". A.M.A. Archives of Internal Medicine 90 (4): 505–512. October 1952. doi:10.1001/archinte.1952.00240100082007. PMID 12975882. 
  77. ↑ "History and development of radiation-protective agents". Int J Radiat Biol 85 (7): 539–573. July 2009. doi:10.1080/09553000902985144. PMID 19557599. "Related research was carried out in the former Soviet Union and other Warsaw Pact countries. [...] Some distinctive compounds studied in these countries included adeturone1, a combination of AET and adenosine triphosphate; other nucleoside derivatives such as riboxine (inosine); and receptor-mediated protective agents such as mexamine and indralin. For many years, meetings of the European Society for Radiation Biology served as a welcome meeting ground for scientists, from the East and West, who were interested in the development of radioprotective agents. [...] Mexamine, a methylated derivative of serotonin and a metabolite of melatonin (N-acetyl-5-methoxytryptamine), has been studied extensively since the 1960s as a radioprotective agent, administered alone or in combination. Radioprotection against lethality in rats was most effective when mexamine was administered IM (Kuna et al. 1983). Mexamine has been shown to provide protection of hematopoietic stem cells (Feher et al. 1968). [...]". 
  78. ↑ "Comparative efficacy and the window of radioprotection for adrenergic and serotoninergic agents and aminothiols in experiments with small and large animals". J Radiat Res 56 (1): 1–10. January 2015. doi:10.1093/jrr/rru087. PMID 25312329. 
  79. ↑ "Protivoluchevaia éffektivnost' meksamina" (in Russian). Med Radiol (Mosk) 19 (1): 74–86. January 1974. PMID 4618322. 
  80. ↑ "Controlled Drugs and Substances Act". https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html. 
  81. ↑ Orange Book: List of Controlled Substances and Regulated Chemicals (January 2026), United States: U.S. Department of Justice: Drug Enforcement Administration (DEA): Diversion Control Division, January 2026, https://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf 



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