The cataleptogenic effects of the neuroleptic nemonapride are attenuated by its 5-HT1A receptor agonist properties.
The effects of the 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)-cycloh exanecarboxamide (WAY 100635) on catalepsy induced by the dopamine D2-like receptor antagonist/5-HT1A receptor agonist nemonapride were examined and compared to its effects on catalepsy induced by neuroleptics that have low affinity for 5-HT1A receptors. Nemonapride induced catalepsy in both cross-legged position and bar tests at low, but not at high doses. Pretreatment with WAY 100635 (0.63 mg/kg) reinstated catalepsy at higher doses of nemonapride, indicating that the 5-HT1A receptor agonist properties of nemonapride are responsible for its inability to produce catalepsy at high doses. Additionally, WAY 100635 enhanced significantly the effects of low doses of nemonapride, and of the dopamine D2-like receptor antagonists raclopride and haloperidol. The present data indicate that the 5-HT1A receptor agonist properties of nemonapride attenuate its ability to induce catalepsy at higher doses, and suggest further that tonic 5-HT1A receptor activation may modulate neuroleptic-induced catalepsy.
Centre de Recherche Pierre Fabre, Castres, France. eric.prinssen@pierre-fabre.com
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D000818:Animals; D014150:Antipsychotic Agents / Q000037:antagonists & inhibitors / Q000633:toxicity; D001549:Benzamides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D002375:Catalepsy / Q000139:chemically induced / Q000517:prevention & control*; D018492:Dopamine Antagonists / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D020891:Raclopride; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D012457:Salicylamides / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D014150:Antipsychotic Agents; D001549:Benzamides; D018492:Dopamine Antagonists; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012457:Salicylamides; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D020891:Raclopride; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D006220:Haloperidol; C030265:nemonapride