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. 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. 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. 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.