title: Anticonvulsant effect of celecoxib on pentylenetetrazole-induced convulsion: Modulation by NO pathway.
abstract: This study aimed to examine whether celecoxib influences clonic seizure thresholds through modulation of nitric oxidergic (NO) pathway. The effect of celecoxib (1-5 mg per kg, p.o.) was investigated on clonic seizures induced by pentylenetetrazole (PTZ, 50 and 80 mg per kg, i.p.) in male Swiss mice. The interaction of celecoxib-induced effects with NO pathway was examined using a NO synthase (NOS) inhibitor, N(G)-omega-nitro-L-arginine methyl ester (L-NAME, 20 and 50 mg per kg, i.p.) and a NOS substrate, L-arginine (100 and 200 mg per kg, i.p.). The criteria for the development of seizure activity were the possibility for appearance of generalized clonus and prolongation of latency to the onset of convulsions following administration of 50 and 80 mg per kg of PTZ, respectively. Pretreatment with celecoxib (2.5 and 5 mg per kg) or L-NAME (50 mg per kg) induced anticonvulsant effect on the PTZ-induced clonic seizures. L-arginine at the dose of 200 mg per kg had proconvulsant effect. A sub-effective dose of celecoxib (1 mg per kg) induced an additive anticonvulsant effect when co-administered with L-NAME (20 mg per kg). Although L-arginine (100 mg per kg) per se did not influence PTZ-induced convulsion, it could attenuate the anticonvulsant effect of celecoxib (5 mg per kg). Our results indicate that celecoxib induces an anticonvulsant effect on clonic seizure threshold that may involve NO pathway.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Zandieh
authors.forename: Farid
authors.initials: F
authors.lastname: Maleki
authors.forename: Alireza
authors.initials: A
authors.lastname: Hajimirzabeigi
authors.forename: Basira
authors.initials: B
authors.lastname: Zandieh
authors.forename: Omid
authors.initials: O
authors.lastname: Khalilzadeh
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001120:Arginine / Q000494:pharmacology; D000068579:Celecoxib; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010433:Pentylenetetrazole / Q000633:toxicity*; D011720:Pyrazoles / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D009569:Nitric Oxide; D001120:Arginine; D000068579:Celecoxib; D019331:NG-Nitroarginine Methyl Ester; D010433:Pentylenetetrazole