Effect of cyclooxygenase-2 (COX-2) inhibitors in various animal models (bicuculline, picrotoxin, maximal electroshock-induced convulsions) of epilepsy with possible mechanism of action.
Enzyme cyclooxygenase (COX) is reported to play a significant role in neurodegeneration and may play a significant role in the pathogenesis of epilepsy. Bicuculline (4 mg/kg; ip), picrotoxin (8 mg/kg; ip) and electroshock (60 mA for 0.2 sec) significantly induced convulsions in male Laka mice. COX-inhibitors viz. nimesulide (2.5 mg/kg; ip) and rofecoxib (2 mg/kg, ip) administered 45 minutes prior to an epileptic challenge prolonged mean onset time of convulsions, decreased duration of clonus and decreased % mortality rate against bicuculline- and picrotoxin-induced convulsions in mice. COX-2 inhibitors were ineffective towards maximal electroshock-induced convulsions. Nimesulide (1 mg/kg) and rofecoxib (1 mg/kg) also enhanced the effect of subprotective dose of muscimol against picrotoxin-induced convulsions. The result of the present study strongly suggests for a possible role of cyclooxygenase isoenzymes particularly, COX-2 in the pathophysiology of epilepsy and its GABAergic modulation.
Dhir
Ashish
A
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Naidu
Pattipati S
PS
Kulkarni
Shrinivas K
SK
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004597:Electroshock / Q000009:adverse effects*; D008297:Male; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced / Q000201:enzymology*
D001640:Bicuculline; D051546:Cyclooxygenase 2; D016861:Cyclooxygenase Inhibitors; D009118:Muscimol; D010852:Picrotoxin