Differential effects of cyclooxygenase inhibitors on haloperidol-induced catalepsy.
Prostaglandins (PGs) might play a role as putative transmitters or as modulators in the central nervous system (CNS). In the present study, haloperidol (1 mg/kg i.p.)-treated mice showed significant cataleptic behaviour. Naproxen, a nonselective cyclooxygenase (COX) inhibitor, dose-dependently (5 and 10 mg/kg) antagonized the haloperidol-induced catalepsy in mice. Nimesulide, a preferential COX inhibitor, also dose-dependently reduced the cataleptic score in haloperidol treated animals at the first and second hour but not at the third and fourth hour of haloperidol treatment. Rofecoxib, a selective COX-2 inhibitor, did not show any effect on haloperidol-induced catalepsy. The major findings of the present study suggest that PGs might play a significant role in haloperidol-induced catalepsy. The findings of the present study further suggested that COX-1 derived rather than COX-2 derived PGs might play a potential role in haloperidol-induced catalepsy. In conclusions COX inhibitors can be screened as potential drug candidates for the treatment of neuroleptic-induced extrapyramidal side effects (EPS).
D000818:Animals; D002375:Catalepsy / Q000139:chemically induced* / Q000188:drug therapy* / Q000201:enzymology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000633:toxicity*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D006220:Haloperidol