title: Amiloride and SN-6 suppress audiogenic seizure susceptibility in genetically epilepsy-prone rats.
abstract: OBJECTIVE
  We have recently reported that amiloride, a potent and nonselective blocker of acid-sensing ion channels, prevents the development of pilocarpine-induced seizures and status epilepticus. Amiloride is also known to suppress the activity of Na(+) /Ca(2+) and Na(+) /H(+) exchangers that have been implicated in the pathophysiology of seizures. Here, we evaluated the effects of amiloride, SN-6 (a potent blocker of Na(+) /Ca(2+) exchangers) and zoniporide (a potent blocker of Na(+) /H(+) exchangers) on acoustically evoked seizures (audiogenic seizures, AGS) in genetically epilepsy-prone rats (GEPR-3s), a model of inherited generalized epilepsy.
  
  
  METHODS
  Male, six-week-old GEPR-3s were used. The GEPR-3s were tested for AGS susceptibility before and after treatment with various doses of amiloride, SN-6, and zoniporide (1, 3, 10, and 30 mg/kg; per os).
  
  
  RESULTS
  We found that pretreatment with amiloride and SN-6 markedly reduced the incidence and severity of AGS in the GEPR-3s. In contrast, administration of zoniporide only minimally reduced the incidence and severity of AGS in the GEPR-3s. A combination of noneffective doses of SN-6 and zoniporide also suppressed AGS susceptibility in the GEPR-3s.
  
  
  CONCLUSIONS
  These findings suggest acid-sensing ion channels and the Na(+) /Ca(2+) exchanger may play an important role in the pathophysiology of inherited AGS susceptibility in the GEPR-3s.
authors.affiliation: Department of Pediatrics, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Hillary
authors.initials: H
authors.lastname: Quansah
authors.forename: Prosper
authors.initials: P
authors.lastname: N'Gouemo
mesh_terms: D000161:Acoustic Stimulation / Q000009:adverse effects; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001593:Benzyl Compounds / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020195:Epilepsy, Reflex / Q000188:drug therapy* / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006146:Guanidines / Q000627:therapeutic use; D008297:Male; D011720:Pyrazoles / Q000627:therapeutic use; D051381:Rats; D055647:Rats, Transgenic; D053778:Thiazolidines / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: C487681:2-(4-(4-nitrobenzyloxy)benzyl)thiazolidine-4-carboxylic acid ethyl ester; D000927:Anticonvulsants; D001593:Benzyl Compounds; D006146:Guanidines; D011720:Pyrazoles; D053778:Thiazolidines; C424422:zoniporide
keywords: Amiloride; Audiogenic seizures; GEPR-3; SN-6; Zoniporide