Amiloride protects against pentylenetetrazole-induced kindling in mice

1 This study was performed to investigate whether or not amiloride, a sodium-hydrogen exchanger (NHE) inhibitor, can protect against seizure development of pentylenetetrazole (PTZ)-induced kindling in mice. 2 Kindling was induced by once every 2 days treatment with PTZ (25 mg kg(-1) i.p.) for 5 weeks. Challenge experiments were carried out after 15 or 30 days of last treatment with PTZ. 3 Administration of amiloride (2 h before PTZ, in doses of 0.65 and 1.3 mg kg(-1), p.o.) significantly prolonged the onset of kindling and reduced the incidence and severity of seizures in a dose-dependent manner. The effect of amiloride on the incidence of PTZ-induced seizures was evident even after 15 or 30 days of last treatment. 4 The results indicate a protective role for amiloride against PTZ-induced kindling in mice. The possibility of mediation of such effects by NHE inhibition is discussed.