O-Pivalylbufotenine

Psychedelic drug From Wikipedia, the free encyclopedia

O-Pivalylbufotenine, or bufotenine O-pivalate, also known as 5-pivaloxy-N,N-dimethyltryptamine (5-t-BuCO-DMT) or as O-pivalyl-N,N-dimethylserotonin, is a synthetic tryptamine derivative and putative serotonergic psychedelic.^[1]^[2]^[3]^[4] It is the O-pivalyl analogue of the naturally occurring but 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]^[4]

Other names5-Pivalylbufotenine; 5-PB; Bufotenine O-pivalate; Bufotenine pivalate; 5-Pivaloxy-N,N-dimethyltryptamine; O-Pivalyl-N,N-dimethylserotonin; 5-t-BuCO-DMT; 5-(tert-BuCO)-DMT

Drug classSerotonin receptor agonist; Serotonergic psychedelic

ATC code

None

PubChem CID

44339071

Quick facts Clinical data, Other names ...

O-Pivalylbufotenine
Clinical data


Other names	5-Pivalylbufotenine; 5-PB; Bufotenine O-pivalate; Bufotenine pivalate; 5-Pivaloxy-N,N-dimethyltryptamine; O-Pivalyl-N,N-dimethylserotonin; 5-t-BuCO-DMT; 5-(tert-BuCO)-DMT
Drug class	Serotonin receptor agonist; Serotonergic psychedelic
ATC code	None
Identifiers
IUPAC name [3-[2-(dimethylamino)ethyl]-1H-indol-5-yl] 2,2-dimethylpropanoate
PubChem CID	44339071
ChemSpider	23195001
ChEMBL	ChEMBL109360
Chemical and physical data
Formula	C₁₇H₂₄N₂O₂
Molar mass	288.391 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CC(C)(C)C(=O)OC1=CC2=C(C=C1)NC=C2CCN(C)C
InChI InChI=1S/C17H24N2O2/c1-17(2,3)16(20)21-13-6-7-15-14(10-13)12(11-18-15)8-9-19(4)5/h6-7,10-11,18H,8-9H2,1-5H3 Key:AFACMZRKVDGTKP-UHFFFAOYSA-N

Use and effects

Interactions

Pharmacology

O-Pivalylbufotenine is thought to be a prodrug of bufotenin and shows psychedelic-like effects in animal.^[3]^[4] However, it is less active than anticipated, perhaps due to its high lipophilicity and, by extension, high plasma protein binding and ester hydrolysis into bufotenin prior to crossing the blood–brain barrier.^[3]^[4] In addition to theoretically acting as a prodrug of bufotenine, which is a non-selective serotonin receptor agonist,^[5]^[6]^[7] O-pivalylbufotenine may also interact directly with certain serotonin receptors.^[4]

Chemistry

Analogues

Analogues of O-pivalylbufotenine (5-t-BuCO-DMT) include bufotenin (5-HO-DMT), 5-MeO-DMT (mebufotenin), and 4-AcO-DMT (psilacetin), among others. In addition, besides O-pivalylbufotenine, other bufotenine O-acyl esters and putative or confirmed bufotenine prodrugs, such as O-acetylbufotenine among others, have been developed and studied.^[1]^[4]

History

O-Pivalylbufotenine was first described in the scientific literature by 1979.^[4]

References

[1]
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].
[2]
Nichols DE, Glennon RA (1984). "Medicinal Chemistry and Structure-Activity Relationships of Hallucinogens". In Jacobs BL (ed.). Hallucinogens: Neurochemical, Behavioral, and Clinical Perspectives. New York: Raven Press. pp. 95–142. ISBN 978-0-89004-990-7. OCLC 10324237. 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).
[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.
[4]
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.
[5]
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.
[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]
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.