Effects of the Calcium Channel Blocker Otilonium Bromide on Seizure Activity in Rats With Pentylenetetrazole-Induced Convulsions.

Abstract

Millions of people suffer from drug-resistant epilepsy. New therapeutic approaches for removing this life-affecting disease are required. The activation of T-type calcium channels (TTCC) is one of the epileptogenesis mechanisms that cause epilepsy. So, we researched the effects of Otilonium bromide (OB), an antisposmolytic drug that inhibits TTCC, on seizure activity in rats with pentylenetetrazol (PTZ) induced convulsion. Randomly, 48 rats were divided into two groups; for electroencephalography (EEG) recordings and for behavioral assesment. Rats were treated with either intraperitoneal (IP) OB at two separate doses (25mg/kg and 50mg/kg) or placebo, and then pentylenetetrazole (IP), a potent seizure-inducing chemical administered to them. In our model we have measured rat seizure activity with EEG, the convulsion scala of Racine (RCS), the time of first myoclonic jerk (FMJ) and MDA levels to assess if OB has antiepileptic properties. The mean EEG spike wave percentage score reduced from 79.5% (placebo) to 59.2% (lower-dose) and 35.2% (higher-dose). FMJ had increased from a mean of 67.2s (placebo), to 105.2 (lower-dose), 150.6 (higher-dose). RCS reduced from a mean of 5.12 (placebo) to 4.4 (lower-dose), 3.8 (higher-dose). MDA leves reduced from 84.5nmol/gr to 51.09nmol/gr (lower-dose), 33.2nmol/gr (higher-dose). Compared to placebo, OB reduced significantly seizure activity at both doses, probably through blocking T-type calcium channels. All these results were statistically significant with < 0.0001 p-values. Otilonium bromide reduced seizure activity in rats with PTZ-induced convulsion. Therefore, the clinical role of OB and other TTCC inhibitors as potential anti-seizure drugs should be further investigated.