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.

Studies To Examine Potential Tolerability Differences between the 5-HT Receptor Selective Agonists Lorcaserin and CP-809101.

Lorcaserin (LOR) is a selective 5-HT receptor agonist that has been FDA approved as a treatment for obesity. The most frequently reported side-effects of LOR include nausea and headache, which can be dose limiting. We have previously reported that in the rat, while LOR produced unconditioned signs characteristic of nausea/malaise, the highly selective 5-HT agonist CP-809101 (CP) produced fewer equivalent signs.