Anticonvulsant Effects of Ivermectin on Pentylenetetrazole- and Maximal Electroshock-Induced Seizures in Mice: The Role of Gabaergic System and Katp Channels Publisher



Manavi MA^{1, 2} ; Mohammad Jafari R¹ ; Shafaroodi H³ ; Ejtemaeimehr S³ ; Sharifzadeh M² ; Dehpour AR^{1, 3} Show Affiliations
Source: Heliyon Published:2022

Abstract

Introduction: Ivermectin (IVM) is an antiparasitic medicine that exerts its function through glutamate-gated chloride channels and GABAA 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 GABAA (diazepam and flumazenil, respectively) as well as KATP 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 GABAA receptors and KATP channels. © 2022 The Author(s)