Additive anticonvulsant effect of flunarizine and sodium valproate on electroshock and chemoshock induced seizures in mice.
The efficacy of Flunarizine (FLU), a calcium channel blocker, in combination with conventional antiepileptic drugs, phenytoin (PHT), carbamazepine (CBZ), sodium valproate (VPA), and ethosuximide (ESM), at ED50 doses, were examined for protective effects against maximal electroshock seizures (MES) and pentylenetetrazol (PTZ) induced seizures in mice. In both models, only VPA and FLU showed significantly enhanced protection, which was additive ie. 100% protection. In the MES test, though FLU combined with PHT did show a slightly enhanced protection (66.6%), with CBZ there was no enhancement as compared to either drug alone. In the PTZ test, FLU with ESM showed 83% protection this however was not statistically significant. The findings of this study in mice suggest that FLU would be a suitable candidate for add-on therapy with VPA for clinical epilepsy.
Joseph
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Department of Pharmacology, St. John's Medical College, Bangalore.
David
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Joseph
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D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D002220:Carbamazepine / Q000627:therapeutic use; D004195:Disease Models, Animal; D004347:Drug Interactions; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004597:Electroshock; D005013:Ethosuximide / Q000627:therapeutic use; D005444:Flunarizine / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010433:Pentylenetetrazole; D010672:Phenytoin / Q000627:therapeutic use; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D014635:Valproic Acid / Q000627:therapeutic use*
D000927:Anticonvulsants; D002220:Carbamazepine; D005013:Ethosuximide; D014635:Valproic Acid; D010672:Phenytoin; D005444:Flunarizine; D010433:Pentylenetetrazole