Correlating the Metabolic Stability of Psychedelic 5-HT2A Agonists with Anecdotal Reports of Human Oral Bioavailability

Sebastian Leth-Petersen; Christoffer Bundgaard; Martin Hansen; Martin A Carnerup; Jan Kehler; Jesper Langgaard Kristensen

doi:10.1007/s11064-014-1253-y

Correlating the Metabolic Stability of Psychedelic 5-HT2A Agonists with Anecdotal Reports of Human Oral Bioavailability

Sebastian Leth-Petersen, Christoffer Bundgaard, Martin Hansen, Martin A Carnerup, Jan Kehler, Jesper Langgaard Kristensen

20 Citations (Scopus)

Abstract

2,5-Dimethoxyphenethylamines and their N-benzylated derivatives are potent 5-HT2A agonists with psychedelic effects in humans. The N-benzylated derivatives are among the most selective 5-HT2A agonists currently available and their usage as biochemical and brain imaging tools is increasing, yet very little is known about the relationships between the structure of the ligands and their pharmacokinetic profile. In order to evaluate the potential of these compounds for in vivo applications we have determined the microsomal stability of 11 phenethylamines and 27 N-benzylated derivatives thereof using human liver microsomes. We found that the N-benzylated phenethylamines have much higher intrinsic clearance than the parent phenethylamines. We hypothesize that their low hepatic stability renders them orally inactive due to first pass metabolism, which is supported by anecdotal data from recreational use of these compounds.

Original language	English
Journal	Neurochemical Research
Volume	39
Issue number	10
Pages (from-to)	2018-2023
Number of pages	6
ISSN	0364-3190
DOIs	https://doi.org/10.1007/s11064-014-1253-y
Publication status	Published - 24 Sept 2014

Access to Document

10.1007/s11064-014-1253-y

Cite this

@article{9fa4bbd6436e4946b04cd0b57255dc7a,

title = "Correlating the Metabolic Stability of Psychedelic 5-HT2A Agonists with Anecdotal Reports of Human Oral Bioavailability",

abstract = "2,5-Dimethoxyphenethylamines and their N-benzylated derivatives are potent 5-HT2A agonists with psychedelic effects in humans. The N-benzylated derivatives are among the most selective 5-HT2A agonists currently available and their usage as biochemical and brain imaging tools is increasing, yet very little is known about the relationships between the structure of the ligands and their pharmacokinetic profile. In order to evaluate the potential of these compounds for in vivo applications we have determined the microsomal stability of 11 phenethylamines and 27 N-benzylated derivatives thereof using human liver microsomes. We found that the N-benzylated phenethylamines have much higher intrinsic clearance than the parent phenethylamines. We hypothesize that their low hepatic stability renders them orally inactive due to first pass metabolism, which is supported by anecdotal data from recreational use of these compounds.",

author = "Sebastian Leth-Petersen and Christoffer Bundgaard and Martin Hansen and Carnerup, {Martin A} and Jan Kehler and Kristensen, {Jesper Langgaard}",

year = "2014",

month = sep,

day = "24",

doi = "10.1007/s11064-014-1253-y",

language = "English",

volume = "39",

pages = "2018--2023",

journal = "Neurochemical Research",

issn = "0364-3190",

publisher = "Springer",

number = "10",

}

TY - JOUR

T1 - Correlating the Metabolic Stability of Psychedelic 5-HT2A Agonists with Anecdotal Reports of Human Oral Bioavailability

AU - Leth-Petersen, Sebastian

AU - Bundgaard, Christoffer

AU - Hansen, Martin

AU - Carnerup, Martin A

AU - Kehler, Jan

AU - Kristensen, Jesper Langgaard

PY - 2014/9/24

Y1 - 2014/9/24

N2 - 2,5-Dimethoxyphenethylamines and their N-benzylated derivatives are potent 5-HT2A agonists with psychedelic effects in humans. The N-benzylated derivatives are among the most selective 5-HT2A agonists currently available and their usage as biochemical and brain imaging tools is increasing, yet very little is known about the relationships between the structure of the ligands and their pharmacokinetic profile. In order to evaluate the potential of these compounds for in vivo applications we have determined the microsomal stability of 11 phenethylamines and 27 N-benzylated derivatives thereof using human liver microsomes. We found that the N-benzylated phenethylamines have much higher intrinsic clearance than the parent phenethylamines. We hypothesize that their low hepatic stability renders them orally inactive due to first pass metabolism, which is supported by anecdotal data from recreational use of these compounds.

AB - 2,5-Dimethoxyphenethylamines and their N-benzylated derivatives are potent 5-HT2A agonists with psychedelic effects in humans. The N-benzylated derivatives are among the most selective 5-HT2A agonists currently available and their usage as biochemical and brain imaging tools is increasing, yet very little is known about the relationships between the structure of the ligands and their pharmacokinetic profile. In order to evaluate the potential of these compounds for in vivo applications we have determined the microsomal stability of 11 phenethylamines and 27 N-benzylated derivatives thereof using human liver microsomes. We found that the N-benzylated phenethylamines have much higher intrinsic clearance than the parent phenethylamines. We hypothesize that their low hepatic stability renders them orally inactive due to first pass metabolism, which is supported by anecdotal data from recreational use of these compounds.

U2 - 10.1007/s11064-014-1253-y

DO - 10.1007/s11064-014-1253-y

M3 - Journal article

C2 - 24519542

SN - 0364-3190

VL - 39

SP - 2018

EP - 2023

JO - Neurochemical Research

JF - Neurochemical Research

IS - 10

ER -

Correlating the Metabolic Stability of Psychedelic 5-HT2A Agonists with Anecdotal Reports of Human Oral Bioavailability

Abstract

Access to Document

Fingerprint

Cite this