5-HT2A/5-HT2C Receptor Pharmacology and Intrinsic Clearance of N-Benzylphenethylamines Modified at the Primary Site of Metabolism

被引：15

作者：

Leth-Petersen, Sebastian ^{[1
]}

Petersen, Ida N. ^{[1
]}

Jensen, Anders A. ^{[1
]}

Bundgaard, Christoffer ^{[2
,3
]}

Baek, Mathias ^{[1
]}

Kehler, Jan ^{[2
,3
]}

Kristensen, Jesper L. ^{[1
]}

机构：

[1] Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, Univ Pk 2, DK-2100 Copenhagen O, Denmark

[2] H Lundbeck & Co AS, Dept Discovery Chem, Ottiliavej 9, DK-2500 Valby, Denmark

[3] H Lundbeck & Co AS, DMPK, Ottiliavej 9, DK-2500 Valby, Denmark

来源：

ACS CHEMICAL NEUROSCIENCE | 2016年 / 7卷 / 11期

关键词：

Phenethylamines; hallucinogens; microsomal stability; 5-HT2A receptor agonists; AGONIST LIGANDS; 5-HT2A; BINDING;

D O I：

10.1021/acschemneuro.6b00265

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 S-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.

引用

页码：1614 / 1619

页数：6

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