Lesopitron is an anxiolytic with pre- and post-synaptic 5-HT1A agonist activity, which is under development by Esteve.
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|Weight||Average: 320.82 |
Intended for the treatment of anxiety disorders.
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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.
|Mechanism of action|
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.
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.
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Hepatic, the main metabolite being 5-hydroxylesopitron.
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1.1 to 5.6 hours
The most commonly reported adverse events in all the panels in one study were headache, dizziness, and nausea [PMID: 8959472].
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|Description||This compound belongs to the class of chemical entities known as n-arylpiperazines. These are organic compounds containing a piperazine ring where the nitrogen ring atom carries an aryl group.|
|Super Class||Organic compounds|
|Alternative Parents||Dialkylarylamines / N-alkylpiperazines / Aminopyrimidines and derivatives / Aryl chlorides / Pyrazoles / Heteroaromatic compounds / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Organochlorides / Hydrocarbon derivatives|
|Substituents||N-arylpiperazine / Dialkylarylamine / Aminopyrimidine / N-alkylpiperazine / Aryl chloride / Aryl halide / Pyrimidine / Pyrazole / Azole / Heteroaromatic compound/ Tertiary aliphatic amine / Tertiary amine / Azacycle / Organopnictogen compound / Organonitrogen compound / Organochloride / Organohalogen compound / Organic nitrogen compound / Amine / Hydrocarbon derivative / Aromatic heteromonocyclic compound|
|Molecular Framework||Aromatic heteromonocyclic compounds|
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- Pharmacological action
- General Function:
- Serotonin receptor activity
- Specific Function:
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G pro...
- Gene Name:
- Uniprot ID:
- Molecular Weight:
- 46106.335 Da