Lesopitron

320.82000

320.82

H1CGM4755H

DTXSID40157587

50.08000

1.93180

1.31g/cm3

504ºC

258.6ºC

1.654

2.77E-10mmHg at 25°C

The most commonly reported adverse events in all the panels in one study were headache, dizziness, and nausea [PMID: 8959472].

Intended for the treatment of anxiety disorders.

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.

Rapidly absorbed in patients, having a time to maximum concentration (Tmax) ranging from 0.5 to 1 hour. The absolute bioavailability of lesopitron in rats was about 10%, suggesting an important first-pass effect.

Hepatic, the main metabolite being 5-hydroxylesopitron.

1.1 to 5.6 hours

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.

2-(4-(4-(4-chloro-1-pyrazolyl)butyl)-1-piperazinyl)pyrimidine