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Experimental evaluation of anticonvulsant activity of calcium channel blocker – cinnarizine alone and in combination with N-methyl-D-aspartate receptor antagonist ketamine in mice

Sharan Kumar K B, Govardhan Reddy Kasireddy, Sruthi Mukkisa, Syeda Ayesha Siddiqua, Sampavan Kumar G.


Background: Epilepsy disease is a chronic condition of the brain affecting the global population and ranked as the world’s second most common neurological disorder, characterized by recurrent seizures. Despite enormous research advances in the treatment field of epilepsy, conventional antiepileptic drugs failed as a better treatment strategy. These limitations emphasized the necessity for exploring the drugs which make the treatment of epilepsy more effective. In our study, cinnarizine, a calcium channel blocker, and Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, are used alone and in combination to evaluate their effectiveness in treating epilepsy by controlling seizures.

Aim and Objectives: The aim of the study was to evaluate the anticonvulsant activity of calcium channel blocker, using cinnarizine alone and in combination with NMDA receptor antagonist ketamine by producing pentylenetetrazol (PTZ)-induced convulsions in male albino mice.

Materials and Methods: Anti-convulsant activity of calcium channel blocker, using cinnarizine alone and in combination with ketamine by producing PTZ induced convulsions in male albino mice species was studied. Institutional Animal Ethics Committee permission was acquired before the commencement of the experimental study. Thrity male albino mice (body weight – 24–40 g) were separated into five groups with the allocation of six mice in each group. Group 1 (Control group) received 0.5 ml distilled H2O, Group 2 (Standard group) received 150 mg/kg of sodium valproate dose, Group 3 (Test group 1) received 30 mg/kg of Cinnarizine, Group 4 (Test group 2) received 50 mg/kg of Ketamine, and Group 5 (Test group 3) received cinnarizine (30 mg/kg) and Ketamine (50 mg/kg) combination. After 30 min of administration of control (0.5 ml distilled water), standard drug, and test drug, male albino mice were injected, PTZ (60 mg/kg), subcutaneously and were monitored. The mean time of onset of convulsion (seconds) mean duration of convulsion, and percentage of protection readings were recorded for 1 h.

Results: Group 1 (Control group) displayed 0% protection from convulsions and Group 2 (Standard group) exhibited 100% and Group 5 (Test group 3) (T3) exhibited 66.66% protection from convulsions, indicating that the combination of cinnarizine (30 mg/kg) and ketamine (50mg/kg) was effective in PTZ-induced seizures in male albino mice.

Conclusion: The anticonvulsant property of cinnarizine and ketamine was less effective when used alone whereas combination was effective, supporting rational use of polytherapy in the treatment of epilepsy.

Key words: Pentylenetetrazol; Sodium Valproate, Cinnarizine; Ketamine; Epilepsy; Anticonvulsant Activity

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