Evaluation of Selective 5-HT 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-HT receptor activation, suggesting that 5-HT receptor activation may have an anticonvulsant property. The present study was designed to evaluate fenfluramine and 5-HT agonists of varying 5-HT agonist selectivity, the relatively nonselective mCPP and Ro 60-0175, and the selective 5-HT 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.