Lorcaserin, a Novel Selective Human 5-Hydroxytryptamine2C Agonist: in Vitro and in Vivo Pharmacological Characterization□S

5-Hydroxytryptamine (5-HT)2C receptor agonists hold promise for the treatment of obesity. In this study, we describe the in vitro and in vivo characteristics of lorcaserin [(1R)-8-chloro-2,3,4,5-tetrahydro-1-methyl-1H-3 benzazepine], a selective, high affinity 5-HT2C full agonist. Lorcaserin bound to human and rat 5-HT2C receptors with high affinity (Ki 15 1 nM, 29 7 nM, respectively), and it was a full agonist for the human 5-HT2C receptor in a functional inositol phosphate accumula-tion assay, with 18- and 104-fold selectivity over 5-HT2A and 5-HT2B receptors, respectively. Lorcaserin was also highly se-lective for human 5-HT2C over other human 5-HT receptors (5-HT1A, 5-HT3, 5-HT4C, 5-HT55A, 5-HT6, and 5-HT7), in addition to a panel of 67 other G protein-coupled receptors and ion channels. Lorcaserin did not compete for binding of ligands to serotonin