Verapamil Interferes With the Anticonvulsant Effect of Morphin in A

Background: opioids exert different effects on seizure threshold based on their dosesand the models. p-glycoprotein (p-gp) prevents various substances from entering thebrain. morphine is a p-gp substrate. the aim of this study was to investigate the effectsof morphine on strychnine-induced convulsion in ovariectomized mice and to seewhether verapamil as a p-gp pump inhibitor interferes with that effects. methods:female mice were ovariectomized to remove the gonadal sex hormones thirtyminutes prior to induction of convulsion by subcutaneous injection of strychnine, theanimals were received morphine (1, 2, 3mg/kg), naloxone (1, 2, 5mg/kg), verapamil(20mg/kg) and morphine (3mg/kg)+verapamil (20mg/kg) intraperitoneally. then, theonset of convulsion and time to death were recorded. the significance of differencesfor the seizure parameters were assessed using one-way analysis of variance(anova) followed by least significant difference (lsd) post hoc comparison orunpaired t-test. results: the results showed that morphine produced anticonvulsanteffect by prolonging the time to death (p < 0.001) and naloxone had no effect onstrychnine-induced convulsion. verapamil alone had no effect on the convulsionwhereas, it significantly (p < 0.05) reduced the anticonvulsant effect of morphine byreducing the time to death. conclusion: anticonvulsant activity of morphine ismediated through different mechanisms. the reduced anticonvulsant effect ofmorphine by verapamil seems to be because of increase in morphine concentration inbrain.