This study aimed to investigate the therapeutic potential of clotrimazole, an inhibitor of the transient receptor potential cation channel, for treating mitochondrial drug-resistant epilepsy and to understand its underlying neurochemical mechanisms. Adult albino mice underwent rotenone-corneal kindling, receiving daily electric shocks (15 mA, 20 V, 6-Hz for 3 s) through a corneal electrode, to induce mitochondrial drug-resistant epilepsy. The onset of drug resistance was confirmed by the significant (p < 0.05) lack of seizure control with standard antiseizure medications including levetiracetam (40 mg/kg), valproate (250 mg/kg), phenytoin (35 mg/kg), lamotrigine (15 mg/kg), and carbamazepine (40 mg/kg). Drug-resistant mice were then classified into one vehicle-treated group and three groups treated with varying doses of clotrimazole (40, 80, and 160 mg/kg orally). Neurochemical analysis of the seizurogenic hippocampus and cerebral cortex was conducted using high-performance liquid chromatography with an electrochemical detector. Administration of clotrimazole alongside standard antiseizure medications led to a significant decrease (p < 0.05) in seizure scores suggesting the restoration of antiseizure effects. Neurochemicals, including tryptophan, serotonin, kynurenine, serine, taurine, gamma-aminobutyric acid, and glutamate, were significantly restored post-clotrimazole treatment. Overall, the present study underscores the adjunct antiseizure effect of clotrimazole in a rotenone corneal kindling mouse model of mitochondrial drug-resistant epilepsy, emphasising its role in neurochemical restoration.
Keywords: Clotrimazole; Drug-resistant epilepsy; Mitochondrial dysfunction; Rotenone corneal kindling; TRPM2 channels.
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