Evaluation of Selective 5-HT2C Agonists in Acute Seizure Models

The 5-HT releaser/reuptake inhibitor fenfluramine has been recently reported to provide benefit as an adjunctive treatment for Dravet and Lennox-Gastaut syndromes, two types of severe childhood epilepsy. Despite its enhancement of 5-HT function, many effects of fenfluramine have been demonstrated to be dependent on 5-HT2C receptor activation, suggesting that 5-HT2C receptor activation may have an anticonvulsant property. The present study was designed to evaluate fenfluramine and 5-HT agonists of varying 5-HT2C agonist selectivity, the relatively nonselective mCPP and Ro 60-0175, and the selective 5-HT2C agonists lorcaserin and CP-809101 across a variety of acute seizure tests conducted in adult rats and mice, which have been instrumental in identifying the majority of clinically efficacious antiepileptic drugs. Tests included the maximal electroshock seizure (MES), MES threshold, and 6 Hz electrical convulsive seizure models and the chemoconvulsant pentylenetetrazole test. The effect of mCPP, lorcaserin,...