A role for ATP-sensitive potassium channels in the anticonvulsant effects of triamterene in mice

•Triamterene delayed clonic seizure in i.v. and i.p. pentylenetetrazole models of mice.•Tonic seizure protection increased after triamterene treatment in ECT model.•A KATP channel blocker, glibenclamide, blocked triamterene effect on seizure.•A KATP channel opener, diazoxide, enhanced anti-seizure effect of triamterene.•KATP channels might be involved in triamterene anti-seizure effect.

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.