Lesopitron (Esteve).
Lesopitron is an anxiolytic with pre- and post-synaptic 5-HT1A agonist activity, which is under development by Esteve [172924, 175197]. It is in phase II trials in Spain [391567, 396196] and the US [396174, 396196]. A series of pilot studies in other indications are also under way [396196]. In phase I trials in healthy volunteers, lesopitron was well tolerated in single doses up to 50 mg, and up to 45 mg/day in repeated doses [234400]. Lesopitron has negligible effects on alpha-adrenergic and dopaminergic receptors [162653], and was more potent than structurally-related 5-HT1A agonists in rat social interaction and marmoset anxiety models. It also countered benzodiazepine withdrawal-induced anxiety in rodents [232978]. The acute toxicity of lesopitron is low and it does not potentiate the effects of alcohol or barbiturates. Long-term usage led to reductions in plasma glucose, triglycerides, phospholipids and cholesterol [232984]. Lesopitron was being developed in collaboration with Knoll Pharmaceuticals [172924, 175197] but this agreement was terminated in December 1995 [394772].
Micheli
F
F
GlaxoSmithKline, Medicines Research Centre, Chemistry Dept, Via Fleming 4, 37135 Verona, Italy. fm20244@glaxowellcome.co.uk