Effects of lesopitron on the central nervous system arising from its interaction with 5-HT1A receptors.
Lesopitron acts as a ligand for central serotonin 5-HT1A receptors. Ki obtained from [3H]8-OH-DPAT competition studies was 104.8 +/- 10.6 nmol/l. As lesopitron did not affect the binding of [3H]paroxetine, involvement of the serotonin reuptake system in the effects of lesopitron is rejected. 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.
Research Centre, Laboratorios Dr. Esteve SA, Barcelona, Spain.
M Angels
MA
Fisas
Antonio
A
Farré
Jorge
J
Camarasa
Elena
E
Escubedo
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D002375:Catalepsy / Q000139:chemically induced; D002490:Central Nervous System / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D007035:Hypothermia / Q000139:chemically induced; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D051379:Mice; D017374:Paroxetine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D058825:Serotonin 5-HT1 Receptor Agonists; D020230:Serotonin Syndrome / Q000139:chemically induced; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013045:Species Specificity
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002492:Central Nervous System Depressants; D008024:Ligands; D017374:Paroxetine; D010879:Piperazines; D011743:Pyrimidines; D058825:Serotonin 5-HT1 Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C075568:lesopitron