Amiloride delays the onset of pilocarpine-induced seizures in rats

Recent evidence suggests that amiloride, a potent and nonselective blocker of acid-sensing ion channels, suppresses generalized seizures induced by maximal electroshock and pentylenetrazole. Here I further determined and quantified the effects of amiloride on the occurrence of limbic seizures and status epilepticus-induced by intraperitoneal administration of pilocarpine, a muscarinic acetylcholine receptor agonist. Pretreatment with various doses (5,10,30, 100, and 200 mg/kg) of amiloride significantly delayed the onset of the first episode of limbic seizures and the occurrence of status epilepticus following administration of pilocarpine (380 mg/kg). At the dose of 100 and 200 mg/kg, amiloride suppressed limbic seizures in 33% of pilocarpine-treated animals and significantly reduced the seizure severity score in 67% of the remaining animals. These findings suggest that amiloride may modulate seizure generation and propagation, probably via mechanisms involving acid-sensing ion channels in the pilocarpine model of temporal lobe epilepsy. (C) 2008 Elsevier B.V. All rights reserved.