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N,N-Dimethyltryptamine is a substituted tryptamine that occurs in many plants and animals, including humans, and which is both a derivative and a structural analog of tryptamine. DMT is used as a psychedelic drug and prepared by various cultures for ritual purposes as an entheogen.
5-Hydroxytryptophan (5-HTP), used medically as oxitriptan, is a naturally occurring amino acid and chemical precursor as well as a metabolic intermediate in the biosynthesis of the neurotransmitter serotonin.
Psilocin, also known as 4-hydroxy-N,N-dimethyltryptamine (4-OH-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic. It is present in most psychedelic mushrooms together with its phosphorylated counterpart psilocybin. Psilocin is a Schedule I drug under the Convention on Psychotropic Substances. Acting on the serotonin 5-HT2A receptors, psilocin's psychedelic effects are directly correlated with the drug's occupancy at these receptor sites. The subjective mind-altering effects of psilocin are highly variable and are said to resemble those of lysergic acid diethylamide (LSD) and N,N-dimethyltryptamine (DMT).
Bufotenin, also known as dimethylserotonin or as 5-hydroxy-N,N-dimethyltryptamine (5-HO-DMT), is a tryptamine derivative, more specifically, a dimethyltryptamine (DMT) analogue, related to the neurotransmitter serotonin. It is an alkaloid found in some species of mushrooms, plants and toads, especially the skin. It is also found naturally in the human body in small amounts.
5-MeO-DET or 5-methoxy-N,N-diethyltryptamine is a hallucinogenic tryptamine.
Psilacetin, also known as O-acetylpsilocin or as 4-acetoxy-N,N-dimethyltryptamine, is a semi-synthetic serotonergic psychedelic drug that has been suggested by David Nichols to be a potentially useful alternative to psilocybin for pharmacological studies, as they are both believed to be prodrugs of psilocin. However, some users report that O-acetylpsilocin's subjective effects differ from those of psilocybin and psilocin. Additionally, some users prefer 4-AcO-DMT to natural psilocybin mushrooms due to feeling fewer adverse side effects such as nausea and heavy body load, which are more frequently reported in experiences involving natural mushrooms. It is the acetylated form of the psilocybin mushroom alkaloid psilocin and is a lower homolog of 4-AcO-MET, 4-AcO-DET, 4-AcO-MiPT and 4-AcO-DiPT.
5,N,N-trimethyltryptamine is a tryptamine derivative that is a psychedelic drug. It was first made in 1958 by Edwin H. P. Young. In animal experiments it was found to be in between DMT and 5-MeO-DMT in potency which would suggest an active dosage for humans in the 20–60 mg range. Human psychoactivity for this compound has been claimed in reports on websites such as Erowid but has not been independently confirmed.
5-MeS-DMT (5-methylthio-N,N-dimethyltryptamine) is a lesser-known psychedelic drug. It is the 5-methylthio analog of dimethyltryptamine (DMT). 5-MeS-DMT was first synthesized by Alexander Shulgin. In his book TiHKAL, the minimum dosage is listed as 15-30 mg. The duration listed as very short, just like DMT. 5-MeS-DMT produces similar effects to DMT, but weaker. Shulgin describes his feelings while on a low dose of this drug as "pointlessly stoned", although at a higher dose of 20 mg he says it is "quite intense" and suggests that a higher dose still might have full activity.
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.
7,N,N-trimethyltryptamine (7-methyl-DMT, 7-TMT), is a tryptamine derivative which acts as an agonist of 5-HT2 receptors. In animal tests, both 7-TMT and its 5-methoxy derivative 5-MeO-7-TMT produced behavioural responses similar to those of psychedelic drugs such as DMT, but the larger 7-ethyl and 7-bromo derivatives of DMT did not produce psychedelic responses despite having higher 5-HT2 receptor affinity in vitro (cf. DOBU, DOAM). 7-TMT also weakly inhibits reuptake of serotonin but with little effect on dopamine or noradrenaline reuptake.
4-MeO-DMT (4-methoxy-N,N-dimethyltryptamine) is a tryptamine derivative which has some central activity in animal tests similar to that of related psychedelic tryptamine drugs, although with significantly lower potency than either 5-MeO-DMT or 4-hydroxy-DMT (psilocin).
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.
Substituted tryptamines, or serotonin 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.
4-Propionoxy-N,N-dimethyltryptamine is a synthetic psychedelic drug from the tryptamine family with psychedelic effects, and is believed to act as a prodrug for psilocin. It produces a head-twitch response in mice. It has been sold online as a designer drug since May 2019. It was first identified as a new psychoactive substance in Sweden, in July 2019. A number of related derivatives have been synthesized as prodrugs of psilocin for medical applications.
5-MeO-MET (5-Methoxy-N-methyl-N-ethyltryptamine) is a relatively rare designer drug from the substituted tryptamine family, related to compounds such as N-methyl-N-ethyltryptamine and 5-MeO-DMT. It was first synthesised in the 1960s and was studied to a limited extent, but was first identified on the illicit market in June 2012 in Sweden. It was made illegal in Norway in 2013, and is controlled under analogue provisions in numerous other jurisdictions.
O-Acetylbufotenine, or bufotenine O-acetate, also known as 5-acetoxy-N,N-dimethyltryptamine (5-AcO-DMT) or O-acetyl-N,N-dimethylserotonin, is a synthetic tryptamine derivative and putative serotonergic psychedelic. It is the O-acetylated analogue of the naturally occurring peripherally selective serotonergic tryptamine bufotenine and is thought to act as a centrally penetrant prodrug of bufotenine.
A neurotransmitter prodrug, or neurotransmitter precursor, is a drug that acts as a prodrug of a neurotransmitter. A variety of neurotransmitter prodrugs have been developed and used in medicine. They can be useful when the neurotransmitter itself is not suitable for use as a pharmaceutical drug owing to unfavorable pharmacokinetic or physicochemical properties, for instance high susceptibility to metabolism, short elimination half-life, or lack of blood–brain barrier permeability. Besides their use in medicine, neurotransmitter prodrugs have also been used as recreational drugs in some cases.
α-Methyltryptophan is a synthetic tryptamine derivative, an artificial amino acid, and a prodrug of α-methylserotonin (αMS). It is the α-methylated derivative of tryptophan, while αMS is the α-methylated analogue of serotonin. αMTP has been suggested for potential therapeutic use in the treatment of conditions thought by some authors to be related to serotonin deficiency, such as depression. In labeled forms, αMTP is also used as a radiotracer in positron emission tomography (PET) imaging to assess serotonin synthesis and certain other processes.
α-Methyl-5-hydroxytryptophan (α-Me-5-HTP) is a synthetic tryptamine derivative, an artificial amino acid, and a prodrug of α-methylserotonin. It is the α-methylated derivative of 5-hydroxytryptophan (5-HTP), while αMS is the α-methylated analogue of serotonin. Along with α-methyltryptophan (α-MTP), α-Me-5-HTP has been suggested for potential therapeutic use in the treatment of conditions thought by some authors to be related to serotonin deficiency, such as depression.
References
- 1 2 3 Glennon RA, Rosecrans JA (1982). "Indolealkylamine and phenalkylamine hallucinogens: a brief overview". Neurosci Biobehav Rev. 6 (4): 489–497. doi:10.1016/0149-7634(82)90030-6. PMID 6757811.
No human studies have been performed with 5-acetoxy bufotenine. Because this acetyl derivative is probably hydrolyzed quite rapidly in vivo, several other 5-acyloxy derivatives have been prepared; detailed pharmacology is not yet available on these compounds, although the pivalyl derivative (5-PB) has been found to be behaviorally active in animals [25].
- 1 2 Nichols DE, Glennon RA (1984). "Medicinal Chemistry and Structure-Activity Relationships of Hallucinogens" (PDF). Hallucinogens: Neurochemical, Behavioral, and Clinical Perspectives. pp. 95–142.
Bufotenine has been found to be behaviorally inactive, or only weakly active, in most animal studies, although at 15 mg/kg, it did produce the head-twitch response in mice (43). It was also behaviorally active in experiments in which the blood-brain barrier was bypassed (78). Acylation of the polar hydroxy group of bufotenine increases its lipid solubility (65, 74) and apparently enhances its ability to cross the blood-brain barrier (64). For example, O-acetylbufotenine (5-acetoxy-N,N-dimethyltryptamine; 54) disrupted conditioned avoidance behavior in rodents (65) and produced tremorigenic activity similar to that elicited by DMT (37) or 5-OMeDMT (59) when administered to mice (64). In this latter study, a comparison of brain levels of bufotenine after administration of O-acetylbufotenine with those of DMT and 5-OMeDMT revealed bufotenine to be the most active of the three agents, based on brain concentration. The pivaloyl ester of bufotenine also appears to possess behavioral activity, since stimulus generalization was observed when this agent was administered to animals trained to discriminate 5-OMeDMT from saline (74).
- 1 2 3 Glennon RA, Rosecrans JA (1981). "Speculations on the mechanism of action of hallucinogenic indolealkylamines". Neurosci Biobehav Rev. 5 (2): 197–207. doi:10.1016/0149-7634(81)90002-6. PMID 7022271.
Yet another compound which is less active than expected is 5-pivalylbufotenine (5-PB) [20]. Although generalization occurs between 5-PB (which possesses twice the 5-HT receptor affinity of 5-OMe DMT) and 5-OMe DMT (20), the ED50 for generalization is 25 μmol/kg. Being a highly lipid-soluble compound, 5-PB may become highly protein bound in vivo and, as a consequence, extensive hydrolysis of the ester linkage may occur prior to penetration of the blood–brain barrier.
- 1 2 3 4 5 6 Glennon RA, Gessner PK, Godse DD, Kline BJ (November 1979). "Bufotenine esters". J Med Chem. 22 (11): 1414–1416. doi:10.1021/jm00197a025. PMID 533890.
Bufotenine (5-hydroxy-N,N-dimethyltryptamine) has been reported to be behaviorally inactive or only very weakly active in man and animals; this may be a consequence of its low partition coefficient and resultant inability to penetrate the blood-brain barrier. The acetyl, propionyl, butyryl, isobutyryl, and pivalyl esters of bufotenine were prepared for future pharmacological evaluation. Unexpectedly, it was found that these esters all possess a relatively high affinity for the serotonin receptors of the isolated rat stomach fundus preparation. A semiquantitative chromatographic measurement of ester hydrolysis suggests that extensive hydrolysis of the esters to bufotenine does not occur under the conditions of the affinity assay.
- ↑ McBride MC (2000). "Bufotenine: toward an understanding of possible psychoactive mechanisms". J Psychoactive Drugs. 32 (3): 321–331. doi:10.1080/02791072.2000.10400456. PMID 11061684.
- ↑ Plazas E, Faraone N (February 2023). "Indole Alkaloids from Psychoactive Mushrooms: Chemical and Pharmacological Potential as Psychotherapeutic Agents". Biomedicines. 11 (2): 461. doi: 10.3390/biomedicines11020461 . PMC 9953455 . PMID 36830997.
- ↑ Neumann J, Dhein S, Kirchhefer U, Hofmann B, Gergs U (2024). "Effects of hallucinogenic drugs on the human heart". Front Pharmacol. 15: 1334218. doi: 10.3389/fphar.2024.1334218 . PMC 10869618 . PMID 38370480.