Blockade of the sodium calcium exchanger exhibits anticonvulsant activity in a pilocarpine model of acute seizures in rats.
Recent evidence suggests that the sodium calcium exchanger (NCX) may contribute to the etiology of pentylenetetrazol-induced seizures. Here we further investigated the role of NCX in the etiology of seizures by quantifying the effects of KB-R7943 and SN-6, potent inhibitors of the reverse mode of NCX subtypes 3 (NCX3) and 1 (NCX1), respectively, on the occurrence of acute seizures and status epilepticus induced by intraperitoneal administration of pilocarpine, a muscarinic acetylcholine receptor agonist. Pretreatment with KB-R7943 significantly reduced the incidence of pilocarpine-induced seizures and status epilepticus in 22-56% of treated animals. In the remaining animals that exhibited seizures, KB-R7943 pretreatment delayed the onset of seizures and status epilepticus, and reduced seizure severity. Delayed onset of seizures and reduced seizure severity also were seen following pretreatment with SN-6. These findings suggest that altered NCX activity may contribute to the pathophysiology of pilocarpine-induced seizures and status epilepticus.
Martinez
Yuris
Y
Department of Pediatrics, Bldg D, Room 285, Georgetown University Medical Center, 3900 Reservoir Rd, NW, Washington DC 20057, USA.
N'Gouemo
Prosper
P
D000208:Acute Disease; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D018721:Muscarinic Agonists / Q000009:adverse effects*; D010862:Pilocarpine / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced* / Q000517:prevention & control; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013890:Thiourea / Q000031:analogs & derivatives / Q000627:therapeutic use
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D000927:Anticonvulsants; D018721:Muscarinic Agonists; D019831:Sodium-Calcium Exchanger; D010862:Pilocarpine; D013890:Thiourea