5‑HT<sub>2A</sub>/5-HT<sub>2C</sub> Receptor
Pharmacology and Intrinsic Clearance of <i>N</i>‑Benzylphenethylamines
Modified at the Primary Site of Metabolism
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<sub>2A</sub>/5-HT<sub>2C</sub> 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-HT<sub>2</sub> receptor agonist
properties, all analogues had an intrinsic clearance above 1.3 L/kg/h
predictive of high first-pass metabolism