5-HT2A/5-HT2C Receptor Pharmacology and Intrinsic Clearance of N-Benzylphenethylamines Modified at the Primary Site of Metabolism.
Sebastian Leth-Petersen, Ida N Petersen, Anders A. Jensen, Christoffer Bundgaard, Mathias Bæk, Jan Kehler, Jesper L. Kristensen
ACS Chemical Neuroscience November 16, 2016 DOI: 10.1021/acschemneuro.6b00265 (opens in new tab) via PubMed
Summary
AI-generated from the abstractThe toxic hallucinogen 25B-NBOMe is rapidly broken down by human liver enzymes and has low oral bioavailability. New chemical variants were synthesized by modifying the part of the molecule where metabolism normally occurs. While some analogues resisted breakdown longer and still strongly activated 5-HT2 receptors, all had an intrinsic clearance above 1.3 L/kg/h, indicating they would still be extensively metabolized on first pass through the liver.
Study at a glance
| Characteristics | Peer reviewed |
|---|---|
| Keywords | 5-ht2a receptor agonists Phenethylamines Hallucinogens Microsomal stability |
| Key finding | All novel analogues of 25B-NBOMe had an intrinsic clearance above 1.3 L/kg/h, predictive of high first-pass metabolism. |
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-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.