Epilepsy Research Today is a free monthly online journal that collates and summarizes the latest research about Epilepsy, including details on symptoms, causes, treatment, drugs, information.

Effect of cyclooxygenase inhibitors on pentylenetetrazol (PTZ)-induced convulsions: Possible mechanism of action.

Dhir A, Naidu PS, Kulkarni SK

Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160014, India.

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.

Published 30 October 2006 in Prog Neuropsychopharmacol Biol Psychiatry, 30(8): 1478-85.
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