Amiloride protects against pentylenetetrazole‐induced kindling in mice

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Abstract
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. 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. 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. 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. British Journal of Pharmacology (2005) 145, 880–884. doi:10.1038/sj.bjp.0706291