Pharma Sci 2020- Effect of Calcium Channel Blockers on the Seizures, Oxidative Stress, and Histoarchitecture in the Rats- Azeezia Institute of Medical Sciences and Research, India

In spite of availability of considerable number of antiepileptic drugs, many patients continue to have seizures that are refractory to treatment defying our understanding and approaches of epilepsy. Many old drugs continue to be evaluated for newer indications. Before such experiments, it is prudent to understand the pathological basis of epilepsy considering many newer understandings. Many of the currently used antiepileptic drugs are shown to inhibit calcium channel activity. Theoretical considerations and few animal model studies have suggested that calcium channel antagonists may play a role as anticonvulsants. These drugs are postulated to inhibit the positive inward burst firing activating wide range of neurons leading to seizures. To support such theoretical considerations, few animal model studies and clinical studies have shown that nimodipine has anticonvulsant property. Combination of calcium channel blockers was shown to have mixed effects. Diltiazem enhances the nimodipine’s antiseizure effects. Flunarizine inhibits nimodipine’s effects. During the last decade of the 20th century, there was a heightened interest in the evaluation of calcium channel blockers for epilepsy in animal model. However after the introduction of gabapentin, topiramate, tiagabine, levetiracetam, and zonisamide, the interest in the evaluation of monotherapy for epilepsy has waned. However, the evaluation has continued as add‑on therapy in both animal model and in clinical trials.

Many animal models have been developed over the previous two decades for evaluation of the novel antiepileptic drugs. The maximal electroshock (MES) model remains as an important gatekeeper for such evaluation, in spite of the fact that it failed in levetiracetam efficacy.  Brain inflammation and brain immune responses play a key role in epilepsy according to recent studies. Oxidative stress mediated by free radicals leading to changes in neuronal structure and function is regarded as possible mechanism of epileptogenesis. Even though the anticonvulsant effects of diltiazem, nimodipine, and flunarizine were previously evaluated, the studies have not concentrated on the neurotransmitter levels and antioxidant effects of these drugs in the rat brain. The objective of the present study was to determine the anticonvulsant effects of these drugs in rat MES model. The study also evaluates the effects on oxidative stress and neurotransmitter levels in rats pretreated with these drugs in MES model. The other objective of the study was to evaluate the acute histological changes in different parts of rats’ brain.

Author(s): K. Saniya

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