Biological Activity
Potent and selective 5-HT 2C receptor agonist (pEC 50 values are 9.96, 7.19 and 6.81 for human 5-HT 2C , 5-HT 2B and 5-HT 2A receptors respectively). Displays antipsychotic activity; suppresses condition avoidance responding (CAR) and inhibits PCP and amphetamine-stimulated hyperactivity in rats following subcutaneous administration.
Biochem/physiol Actions
CP-809,101 is a potent and high-affinity 5-hydroxytryptamine receptor 2C (5-HT2C) full agonist with only weaker partial agonist activity toward 5-HT2A & 5-HT2B (cellular Ca2+ mobilization EC50 in nM/efficiency = 0.11/93% and 0.06/97% with human and rat 5-HT2C, respectively; 153/67%/human 5HT2A, 65.3/57%/human 5HT2B, 119/79%/rat 5HT2A) and much reduced or little affinity toward other receptors, ion channels and uptake sites tested. CP-809,101 exhibits antipsychotic efficacy in reducing conditioned avoidance response/CAR (ED50 = 4.8 mg/kg s.c.) and locomotor activity (ED50 in mg/kg via s.c. = 2/rats, 1/mice; no effect up to 10 mg/kg in 5-HT2C-knockout mice), while oral administration is reported to suppress spontaneous and nocturnal food intake as well as fasting-induced refeeding in rats (～8% and ～24% reduction of cumulative food intake and body weight in 4 days, respectively; 30 mg/kg/day p.o.).
