Anticonvulsant action of celecoxib (alone and in combination with sub-threshold dose of phenytoin) in electroshock induced convulsion.
Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor, COX-2 has been shown to be upregulated by convulsive nerve activity. Various earlier studies have given conflicting reports on the effect of COX inhibitors on seizures. This study investigates the effect of pretreatment with celecoxib alone, or in combination with phenytoin, on electroshock-induced convulsions. Both percentage protection (i.e., the percentage of animals not showing Tonic Hind Limb Extension [THLE] when a fixed dose of current is administered) and CC50 (i.e., the threshold current inducing THLE in 50%) was determined using a technoconvulsometer. Celecoxib and phenytoin were administered 1 and 2 h, respectively, prior to the experiments. When administered alone, celecoxib showed an increase in percentage protection at increasing doses, with maximum percentage protection (66.6%) occurring at a 30 mg/kg-1 dose. The ED25 value of celecoxib was calculated to be 8.03 mg/kg-1. The CC50 values for the treatment groups were significantly increased compared with the control group (CC50 values for control, celecoxib 10 mg/kg-1, celecoxib 20 mg/kg-1 and celecoxib 30 mg/kg-1, respectively, were 36.3, 49.12, 100.3 and 125.02 mA). An increase in percentage protection was noted when celecoxib 8.03 mg/kg-1 was coadministered with phenytoin 6 mg/kg-1 (66.6% with the combination vs. 16.6% when administered individually). A significant increase was noted in the CC50 value in a combination regimen (CC50 = 79.06) compared with either drug administered alone (CC50 = 49.12 with celecoxib 8.03 mg/kg-1 and 62.06 with phenytoin 6 mg/kg-1). This study may stimulate further interest in the role of COX-2 inhibitors in the modulation of seizure activity.
Department of Pharmacology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
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Shafiq
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Malhotra
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Pandhi
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004597:Electroshock; D008297:Male; D010672:Phenytoin / Q000008:administration & dosage / Q000494:pharmacology*; D011720:Pyrazoles; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*
D000927:Anticonvulsants; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D010672:Phenytoin; D000068579:Celecoxib