title: A role for ATP-sensitive potassium channels in the anticonvulsant effects of triamterene in mice.
abstract: There are reports indicating that diuretics including chlorothiazide, furosemide, ethacrynic acid, amiloride and bumetanide can have anticonvulsant properties. Intracellular acidification appears to be a mechanism for the anticonvulsant action of some diuretics. This study was conducted to investigate whether or not triamterene, a K(+)-sparing diuretic, can generate protection against seizures induced by intravenous or intraperitoneal pentylenetetrazole (PTZ) models. And to see if, triamterene can withstand maximal electroshock seizure (MES) in mice. We also investigated to see if there is any connection between triamterene's anti-seizure effect and ATP-sensitive K(+) (KATP) channels. Five days triamterene oral administration (10, 20 and 40 mg/kg), significantly increased clonic seizure threshold which was induced by intravenous pentylenetetrazole. Triamterene (10, 20 and 40 mg/kg) treatment also increased the latency of clonic seizure and decreased its frequency in intraperitoneal PTZ model. Administration of triamterene (20 mg/kg) also decreased the incidence of tonic seizure in MES-induced seizure. Co-administration of a KATP sensitive channel blocker, glibenclamide, in the 6th day, 60 min before intravenous PTZ blocked triamterene's anticonvulsant effect. A KATP sensitive channel opener, diazoxide, enhanced triamterene's anti-seizure effect in both intravenous PTZ or MES seizure models. At the end, triamterene exerts anticonvulsant effect in 3 seizure models of mice including intravenous PTZ, intraperitoneal PTZ and MES. The anti-seizure effect of triamterene probably is induced through KATP channels.
authors: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Branch and Pharmaceutical Sciences Research Center, Islamic Azad University, Tehran, Iran.
authors: Hamed
authors: H
authors: Shafaroodi
authors: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Branch and Pharmaceutical Sciences Research Center, Islamic Azad University, Tehran, Iran.
authors: Saghar
authors: S
authors: Barati
authors: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors: Mehdi
authors: M
authors: Ghasemi
authors: Department of Medicinal Chemistry, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran.
authors: Ali
authors: A
authors: Almasirad
authors: Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Nanomedicine and Nanobiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: moezile@yahoo.com.
authors: Leila
authors: L
authors: Moezi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D003292:Convulsants / Q000633:toxicity; D003981:Diazoxide / Q000008:administration & dosage; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D004597:Electroshock / Q000009:adverse effects; D005905:Glyburide / Q000008:administration & dosage; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000633:toxicity; D026902:Potassium Channel Blockers / Q000627:therapeutic use; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology; D014223:Triamterene / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D003292:Convulsants; D026902:Potassium Channel Blockers; D003981:Diazoxide; D005905:Glyburide; D010433:Pentylenetetrazole; D014223:Triamterene
keywords: K(ATP) channels; Maximal electroshock; Mice; Pentylenetetrazole; Seizure; Triamterene