VERAPAMIL INTERFERES WITH THE ANTICONVULSANT EFFECT OF MORPHIN IN A STRYECHNINE INDUCED CONVULSION MODEL IN MICE

Opioids exert different effects on seizure threshold based on their doses and the models. P-glycoprotein (p-gp) prevents various substances from entering the brain. Morphine is a p-gp substrate. The aim of this study was to investigate the effects of morphine on strychnine-induced convulsion in ovariectomized mice and to see whether verapamil as a p-gp pump inhibitor interferes with that effects Methods: Female mice were ovariectomized to remove the gonadal sex hormones Thirty minutes prior to induction of convulsion by subcutaneous injection of strychnine, the animals were received morphine (1, 2, 3mg/kg), naloxone (1, 2, 5mg/kg), verapamil (20mg/kg) and morphine (3mg/kg)+verapamil (20mg/kg) intraperitoneally. Then, the onset of convulsion and time to death were recorded. The significance of differences for the seizure parameters were assessed using one-way analysis of variance (ANOVA) followed by least significant difference (LSD) post hoc comparison or unpaired t-test. Results: The results showed that morphine produced anticonvulsant effect by prolonging the time to death (P < 0.001) and naloxone had no effect on strychnine-induced convulsion. Verapamil alone had no effect on the convulsion whereas, it significantly (p < 0.05) reduced the anticonvulsant effect of morphine by reducing the time to death. Conclusion: Anticonvulsant activity of morphine is mediated through different mechanisms. The reduced anticonvulsant effect of morphine by verapamil seems to be because of increase in morphine concentration in brain.