O-Acetylbufotenine

Last updated
O-Acetylbufotenine
5-AcO-DMT.svg
Clinical data
Other namesO-Acetylbufotenin; Bufotenine acetate; Bufotenin acetate; Bufotenine O-acetate; Bufotenin O-acetate; 5-Acetoxy-N,N-dimethyltryptamine; 5-Acetoxy-DMT; 5-AcO-DMT; 5-Acetoxy-N,N-DMT; O-Acetyl-N,N-dimethylserotonin
Drug class Serotonin receptor agonist; Serotonergic psychedelic
Identifiers
  • [3-[2-(dimethylamino)ethyl]-1H-indol-5-yl] acetate
CAS Number
PubChem CID
ChemSpider
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C14H18N2O2
Molar mass 246.310 g·mol−1
3D model (JSmol)
  • CC(=O)OC1=CC2=C(C=C1)NC=C2CCN(C)C
  • InChI=1S/C14H18N2O2/c1-10(17)18-12-4-5-14-13(8-12)11(9-15-14)6-7-16(2)3/h4-5,8-9,15H,6-7H2,1-3H3
  • Key:BZFGYTBVFYYKOK-UHFFFAOYSA-N

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. [1] [2] [3] It is the O-acetylated analogue of the naturally occurring peripherally selective serotonergic tryptamine bufotenine (5-hydroxy-N,N-dimethyltrypamine or N,N-dimethylserotonin) and is thought to act as a centrally penetrant prodrug of bufotenine. [1] [2] [3]

Bufotenine has low lipophilicity, limitedly crosses the blood–brain barrier in animals, does not produce psychedelic-like effects in animals except at very high doses or administered directly into the brain, and produces inconsistent and weak psychedelic effects accompanied by pronounced peripheral side effects in humans. [1] [4] [5] [3] O-Acetylbufotenine, which is much more lipophilic than bufotenine due to its acetyl group, was developed in an attempt to overcome bufotenine's limitations and allow for the drug to efficiently cross the blood–brain barrier. [1] [3] In contrast to peripherally administered bufotenine, O-acetylbufotenine readily enters the brain in animals and produces robust psychedelic-like effects. [1] [2] In addition, O-acetylbufotenine was more potent than N,N-dimethyltryptamine (DMT) or 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; O-methylbufotenine) in animals. [1] [2] However, the effects of O-acetylbufotenine in humans have not been assessed or reported. [1] Alexander Shulgin speculated about O-acetylbufotenine in TiHKAL but did not personally synthesize or test it. [3]

O-Acetylbufotenine is thought to be a prodrug of bufotenine, which is a non-selective agonist of many of the serotonin receptors, including of the serotonin 5-HT2A receptor (the activation of which is associated with psychedelic effects). [4] [6] [5] However, O-acetylbufotenine has also unexpectedly been found to act directly as an agonist of certain serotonin receptors, including of the serotonin 5-HT1A and 5-HT1D receptors. [7] [8]

The O-acetyl substitution of O-acetylbufotenine is expected to be cleaved quite rapidly in vivo , which may hinder the ability of O-acetylbufotenine to cross the blood–brain barrier and deliver bufotenine into the central nervous system. [1] Because of this, other O-acyl derivatives of bufotenine besides O-acetylbufotenine have been developed and studied. [1] [7] One such analogue, O-pivalylbufotenine, has been assessed and has likewise been shown to produce psychedelic-like effects animals. [1] [2] [7]

O-Acetylbufotenine was first described in the scientific literature by 1968. [9] [10]

See also

Related Research Articles

<i>N</i>,<i>N</i>-Dimethyltryptamine Chemical compound

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.

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

5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), also known as O-methylbufotenin or mebufotenin, is a naturally occurring psychedelic of the tryptamine family. It is found in a wide variety of plant species, and is also secreted by the glands of at least one toad species, the Colorado River toad. It may occur naturally in humans as well. Like its close relatives dimethyltryptamine (DMT) and bufotenin (5-HO-DMT), it has been used as an entheogen in South America. Slang terms include Five-methoxy, the power, bufo, and toad venom.

<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">Bufotenin</span> Psychedelic drug found in toads, mushrooms and plants

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.

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

5-MeO-MiPT is a psychedelic and hallucinogen of the tryptamine family. It used by some as an entheogen. It has structural and pharmacodynamic properties similar to the drugs 5-MeO-DiPT, DiPT, and MiPT. It is commonly used as a "substitute" for 5-MeO-DiPT because of the very similar structure and effects.

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

5-MeO-DET or 5-methoxy-N,N-diethyltryptamine is a hallucinogenic tryptamine.

<i>N</i>-Methyltryptamine Chemical compound

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.

<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.

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

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.

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

5-Fluoro-N,N-dimethyltryptamine is a tryptamine derivative related to compounds such as 5-bromo-DMT and 5-MeO-DMT. It produces a robust head-twitch response in mice, and hence is a putative serotonergic psychedelic. Fluorination of psychedelic tryptamines either reduces or has little effect on 5-HT2A/C receptor affinity or intrinsic activity, although 6-fluoro-DET is inactive as a psychedelic despite acting as a 5-HT2A agonist, while 4-fluoro-5-methoxy-DMT is a much stronger agonist at 5-HT1A than 5-HT2A.

5-Methoxy-7,<i>N</i>,<i>N</i>-trimethyltryptamine Chemical compound

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<span class="mw-page-title-main">7,N,N-TMT</span> Chemical compound

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<span class="mw-page-title-main">4-MeO-DMT</span> Chemical compound

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).

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

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.

<span class="mw-page-title-main">Neurotransmitter prodrug</span> A prodrug of a neurotransmitter

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.

<i>O</i>-Pivalylbufotenine Tryptamine serotonergic psychedelic

O-Pivalylbufotenine, or bufotenine O-pivalate, also known as 5-pivaloxy-N,N-dimethyltryptamine or O-pivalyl-N,N-dimethylserotonin, is a synthetic tryptamine derivative and putative serotonergic psychedelic. It is the O-pivalyl analogue of the naturally occurring but peripherally selective serotonergic tryptamine bufotenine and is thought to act as a centrally penetrant prodrug of bufotenine.

<span class="mw-page-title-main">6-MeO-DMT</span> Non-hallucinogenic 5-HT2A agonist

6-MeO-DMT, or 6-methoxy-N,N-dimethyltryptamine, also known as 6-OMe-DMT, is a serotonergic drug of the tryptamine family. It is the 6-methoxy derivative of the serotonergic psychedelic N,N-dimethyltryptamine (DMT) and is a positional isomer of the serotonergic psychedelic 5-MeO-DMT.

<span class="mw-page-title-main">6-MeO-isoDMT</span> Serotonergic psychoplastogen

6-MeO-isoDMT, or 6-OMe-isoDMT, also known as 6-methoxy-N,N-dimethylisotryptamine, is a serotonin 5-HT2A receptor agonist, putative serotonergic psychedelic, and psychoplastogen of the isotryptamine group. It is the isotryptamine analogue of the psychedelic 5-MeO-DMT and is a positional isomer of the non-hallucinogenic psychoplastogen 5-MeO-isoDMT.

isoDMT Serotonergic drug

isoDMT, also known as N,N-dimethylisotryptamine, is a putatively non-hallucinogenic serotonin 5-HT2A receptor agonist and psychoplastogen of the isotryptamine group. It is the isotryptamine homologue of dimethyltryptamine (DMT), a more well-known serotonergic psychedelic of the tryptamine family, and represents a small structural modification of DMT.

References

  1. 1 2 3 4 5 6 7 8 9 10 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. In an effort to overcome this problem of poor lipid solubility, Gessner et al. [20] prepared 5-acetoxy DMT (i.e., O-acetyl bufotenine), which was found to possess a greater lipid solubility than bufotenine, and, which should be hydrolyzed to bufotenine once it has entered the brain. Animal studies reveal that 5-acetoxy DMT is behaviorally active, and more active than either DMT or 5-OMe DMT [17]. No human studies have been performed with 5-acetoxy bufotenine.
  2. 1 2 3 4 5 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 resonse 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).
  3. 1 2 3 4 5 Shulgin & Shulgin. TiHKAL #19. 5-HO-DMT
  4. 1 2 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.
  5. 1 2 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.
  6. ↑ 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.
  7. 1 2 3 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.
  8. ↑ Glennon RA, Hong SS, Bondarev M, Law H, Dukat M, Rakhi S, Power P, Fan E, Kinneau D, Kamboj R, Teitler M, Herrick-Davis K, Smith C (January 1996). "Binding of O-alkyl derivatives of serotonin at human 5-HT1D beta receptors". Journal of Medicinal Chemistry. 39 (1): 314–22. doi:10.1021/jm950498t. PMID   8568822.
  9. ↑ Gessner PK, Godse DD, Krull AH, McMullan JM (March 1968). "Structure-activity relationships among 5-methoxy-n:n-dimethyltryptamine, 4-hydroxy-n:n-dimethyltryptamine (psilocin) and other substituted tryptamines". Life Sci. 7 (5): 267–77. doi:10.1016/0024-3205(68)90200-2. PMID   5641719.
  10. ↑ Gessner PK, Dankova JB (January 1975). "Brain Bufotenine from Administered Acetylbufotenine: Comparison of Its Tremorgenic Activity with That of N,N-Dimethyltryptamine and 5-Methoxy-N,N-Dimethyltryptamine". Pharmacologist. 17 (2): 259.


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