Anticonvulsant Effects of Ivermectin on Pentylenetetrazole- and Maximal Electroshock-induced Seizures in Mice: the Role of GABAergic System and K Channels

Introduction: Ivermectin (IVM) is an antiparasitic medicine that exerts its function through glutamate-gated chloride channels and GABA receptors predominantly. There is paucity of information on anti-seizure activity of IVM. Moreover, the probable pharmacological mechanisms underlying this phenomenon have not been identified.

Materials And Methods: In this study, pentylenetetrazole (PTZ)-induced clonic seizures and maximal electroshock (MES)-induced tonic-clonic seizure models, respectively in mice was utilized to inquire whether IVM could alter clonic seizure threshold (CST) and seizure susceptibility. To assess the underlying mechanism behind the anti-seizure activity of IVM, we used positive and negative allosteric modulators of GABA (diazepam and flumazenil, respectively) as well as K channel opener and closer (cromakalim and glibenclamide, respectively). Data are provided as mean ± S.E.M. After the performance of the variance homogeneity test, a one-way and two-way analysis of variance was used. Fisher's exact test was performed in case of MES. P-value less than 0.05 considered statistically significant.

Results: and Discussion: Our data showed that IVM (0.5, 1, 5, and 10 mg/kg, i.p.) increased CST. Furthermore, flumazenil 0.25 mg/kg, i.p. and glibenclamide 1 mg/kg, i.p., could inhibit the anticonvulsant effects of IVM. Supplementary, an ineffective dose of diazepam 0.02 mg/kg, i.p. or cromakalim 10 μg/kg, i.p. were able to enhance the anticonvulsant effects of IVM. Besides, we figure out that the IVM (1 and 5 mg/kg, i.p.) could delay the onset of first clonic seizure and also might decrease the frequency of clonic seizures induced by PTZ (85 mg/kg, i.p.). Finally, IVM could prevent the incidence and death in MES-induced tonic-clonic seizures.

Conclusion: Based on the obtained results, it can be concluded that IVM may exert anticonvulsant effects against PTZ- and MES-induced seizures in mice that might be mediated by GABA receptors and K channels.