Lorcaserin is approved by the Food and Drug Administration for treating obesity and its therapeutic effects are thought to result from agonist activity at serotonin (5-HT)2C receptors. Lorcaserin has affinity for other 5-HT receptor subtypes, although its activity at those subtypes is not fully described. The current study compared the behavioral effects of lorcaserin (0.0032-32.0 mg/kg) to the effects of other 5-HT receptor selective agonists in rats (n=8). The 5-HT2C receptor selective agonist mCPP (0.032 - 1.0 mg/kg) and lorcaserin induced yawning that was attenuated by the 5-HT2C receptor selective antagonist SB 242084 (1.0 mg/kg). The 5-HT2A receptor selective agonist DOM (0.1-3.2 mg/kg) induced head twitching that was attenuated by the 5-HT2A receptor selective antagonist MDL 100907 (0.01 mg/kg), lorcaserin (3.2 mg/kg), and mCPP (3.2 mg/kg). In rats pretreated with 5-HT2C SB 242084 (1.0 mg/kg), lorcaserin also induced head twitching. At larger doses, lorcaserin produced forepaw treading that was attenuated by the 5-HT1A receptor selective antagonist WAY 100635 (0.178 mg/kg). While the behavioral effects of lorcaserin in rats are consistent with it having agonist activity at 5-HT2C receptors, these data suggest that, at larger doses, it also has agonist activity at 5-HT2A and possibly 5-HT1A receptors. Mounting evidence suggests that 5-HT2C receptor agonists might be effective for treating drug abuse. A more complete description of the activity of lorcaserin at 5-HT receptor subtypes will facilitate a better understanding of the mechanisms that mediate its therapeutic effects.
- The American Society for Pharmacology and Experimental Therapeutics