Nifedipine inhibits picrotoxin-induced seizure activity: further evidence on the involvement of L-type calcium channel blockers in epilepsy.
A large body of evidence supports the role of L-type calcium channels in epileptogenesis. The aim of the present study was to study the efficacy of the specific L-type calcium channel blocker nifedipine on seizure activity induced by picrotoxin (PTX). Adult female Sprague-Dawley rats were used in these experiments. The intraperitoneal administration of nifedipine (5 mg/kg) did not significantly alter the latency to onset of clonic seizure induced by intraperitoneal injection of PTX (4 mg/kg). Higher doses of the drug (10 and 20 mg/kg) significantly increased the latency of onset of clonic seizure in a dose-dependent manner. Nifedipine (10 mg/kg) did not reduce the incidence of clonic seizures in the animals injected with PTX, but inhibited tonic seizure and the progression of clonic seizures into maximal tonic seizures in four of eight of the animals. The drug (20 mg/kg) inhibited clonic seizure in four of six of the animals and abolished minimal or maximal tonic seizures in all the animals. In conclusion, our study provides further evidence on the antiepileptic effect of L-type calcium channel blocker nifedipine by showing its protective effect on seizure activity induced by PTX.
Department of Pharmacology, Faculty of Medicine, Arabian Gulf University, PO Box 22979, Bahrain. sotoom@rcsi-mub.com
Sameer
S
Otoom
Zuhair
Z
Hasan
D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D020746:Calcium Channels, L-Type / Q000502:physiology*; D003292:Convulsants; D004305:Dose-Response Relationship, Drug; D005260:Female; D009543:Nifedipine / Q000627:therapeutic use*; D010852:Picrotoxin; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D003292:Convulsants; D009543:Nifedipine; D010852:Picrotoxin