New Antidementia Molecules Which Selectively Influence Serotonin Receptor Subtypes

Abstract

A battery of animal tests is described which have allowed the detection of novel compounds which can inhibit memory impairments. The compounds include selective 5-HT₃receptor antagonists such as ondansetron, zacopride, and tropisetron, and certain new ligands for the 5-HT_Areceptor, including lesopitron. The preclinical tests which have been employed have included a mouse habituation model, rat T-maze and water maze tests, and a primate object discrimination and reversal task. Impairments have been induced by scopolamine and by lesions of the nucleus basalis magnocellularis, and the natural impairments associated with old age have also been assessed. The abilities of the 5-HT₃receptor antagonists to inhibit memory impairments may relate to an ability to inhibit a reduced acetylcholine release, as indicated by biochemical experiments, and this would form a correlate with the cholinergic hypothesis describing memory disorders. Initial clinical trials have investigated the potential of ondansetron to improve Age Associated Memory Impairments. The data has been sufficiently encouraging to provide a validity for the animal studies.