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.
Department of Pediatrics and Pharmacology, Georgetown University Medical Center, 3900 Reservoir Road NW, Washington, DC 20057, USA. pn@georgetown.edu
Prosper
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N'Gouemo
D000584:Amiloride / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D010862:Pilocarpine; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D026941:Sodium Channel Blockers / Q000627:therapeutic use*
D026941:Sodium Channel Blockers; D010862:Pilocarpine; D000584:Amiloride