5-HT2A/5-HT2C receptor pharmacology and intrinsic clearance of N-benzylphenethylamines modified at the primary site of metabolism

Sebastian Leth-Petersen; Ida Nymann Petersen; Anders A Jensen; Christoffer Bundgaard; Mathias Bæk; Jan Kehler; Jesper L Kristensen

doi:10.1021/acschemneuro.6b00265

5-HT2A/5-HT2C receptor pharmacology and intrinsic clearance of N-benzylphenethylamines modified at the primary site of metabolism

Sebastian Leth-Petersen, Ida Nymann Petersen, Anders A Jensen, Christoffer Bundgaard, Mathias Bæk, Jan Kehler, Jesper L Kristensen

9 Citations (Scopus)

Abstract

The toxic hallucinogen 25B-NBOMe is very rapidly degraded by human liver microsomes and has low oral bioavailability. Herein we report on the synthesis, microsomal stability, and 5-HT_2A/5-HT_2C receptor profile of novel analogues of 25B-NBOMe modified at the primary site of metabolism. Although microsomal stability could be increased while maintaining potent 5-HT₂ receptor agonist properties, all analogues had an intrinsic clearance above 1.3 L/kg/h predictive of high first-pass metabolism.

Original language	English
Journal	A C S Chemical Neuroscience
Pages (from-to)	1-6
Number of pages	6
ISSN	1948-7193
DOIs	https://doi.org/10.1021/acschemneuro.6b00265
Publication status	Published - 16 Nov 2016

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10.1021/acschemneuro.6b00265

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T1 - 5-HT2A/5-HT2C receptor pharmacology and intrinsic clearance of N-benzylphenethylamines modified at the primary site of metabolism

AU - Leth-Petersen, Sebastian

AU - Petersen, Ida Nymann

AU - Jensen, Anders A

AU - Bundgaard, Christoffer

AU - Bæk, Mathias

AU - Kehler, Jan

AU - Kristensen, Jesper L

PY - 2016/11/16

Y1 - 2016/11/16

N2 - The toxic hallucinogen 25B-NBOMe is very rapidly degraded by human liver microsomes and has low oral bioavailability. Herein we report on the synthesis, microsomal stability, and 5-HT2A/5-HT2C receptor profile of novel analogues of 25B-NBOMe modified at the primary site of metabolism. Although microsomal stability could be increased while maintaining potent 5-HT2 receptor agonist properties, all analogues had an intrinsic clearance above 1.3 L/kg/h predictive of high first-pass metabolism.

AB - The toxic hallucinogen 25B-NBOMe is very rapidly degraded by human liver microsomes and has low oral bioavailability. Herein we report on the synthesis, microsomal stability, and 5-HT2A/5-HT2C receptor profile of novel analogues of 25B-NBOMe modified at the primary site of metabolism. Although microsomal stability could be increased while maintaining potent 5-HT2 receptor agonist properties, all analogues had an intrinsic clearance above 1.3 L/kg/h predictive of high first-pass metabolism.

U2 - 10.1021/acschemneuro.6b00265

DO - 10.1021/acschemneuro.6b00265

M3 - Journal article

C2 - 27564969

SN - 1948-7193

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JO - A C S Chemical Neuroscience

JF - A C S Chemical Neuroscience

ER -

5-HT2A/5-HT2C receptor pharmacology and intrinsic clearance of N-benzylphenethylamines modified at the primary site of metabolism

Abstract

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