Cyclooxygenase (COX) is reported to play a significant role in neurodegenerative and neuropsychiatric disorders, and may play a significant role in the pathogenesis of
epilepsy. Various
neurotransmitter abnormalities, especially of
GABA and
glutamate, have been reported to play a key role in the pathophysiology of
epilepsy. The objective of the present study was to elucidate the effect of
cyclooxygenase inhibitors on
pentylenetetrazol (PTZ)-induced (80 mg/kg) convulsions in mice with possible mechanism of action. Various COX-inhibitors were administered 45 min prior to the PTZ administration. Onset, duration of clonic convulsions and percentage mortality/recovery were recorded. Pretreatment with COX-inhibitors
aspirin (10 and 20 mg/kg, p.o.),
naproxen (7 and 14 mg/kg, p.o.),
nimesulide (1-5 mg/kg, p.o.) or
rofecoxib (1-4 mg/kg, p.o.) dose-dependently showed protection against PTZ-induced convulsions.
COX-2 inhibitors were more effective as compared to non-selective COX-inhibitors.
Rofecoxib (1 mg/kg) or
nimesulide (1 mg/kg) also enhanced the sub-protective effect of
diazepam or
muscimol showing GABAergic modulation of
COX-2 inhibitors.
COX-2 inhibitors also antagonized the effect of
flumazenil (4 mg/kg)- against PTZ-induced convulsions further confirming the GABAergic mechanism. In conclusion, the results of the present study strongly suggest the possible role of
cyclooxygenase isoenzymes in the pathophysiology of
epilepsy and the use of COX-inhibitors as an adjuvant
therapy in the treatment of
epilepsy.