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Pharm Sci. 2013;19(3): 69-75.
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Original Research

Verapamil Interferes With the Anticonvulsant Effect of Morphin in A Stryechnine Induced Convulsion Model in Mice

fahimeh hassanvand * , Lotfolah Khajepour, Hossein Najafzadeh-Varzi

Abstract

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.
Keywords: morphine, naloxone, verapamil, strychnine, mice
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Submitted: 22 Nov 2013
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