Lesopitron

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. Lesopitron has negligible effects on alpha-adrenergic and dopaminergic receptors, 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. 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.

Lesopitron acts as a ligand for central serotonin 5-HT1A receptors. Lesopitron inhibits haloperidol-induced catalepsy that is the consequence of its action on 5-HT1A autoreceptors. The ability of lesopitron to induce 5-HT syndrome reflects post-synaptic 5-HT1A receptor activation and the reversion of 8-OHDPAT-induced 5-HT syndrome by lesopitron suggests a partial agonist effect on this receptor-type. Lesopitron induced a hypothermic effect due to the enhanced activation of post-synaptic 5-HT1A receptors. The agonist effect of lesopitron on 5-HT1A receptors and its marked hypothermic effect is an added value for this drug and a stimulus to the study of its possible neuroprotective action.