Effects between the first-and second-generation histamine H1-antagonists on seizure development of pentylenetetrazole-induced kindling in rats / 浙江大学学报·医学版

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects and the mechanisms of the first-generation histamine H(1)-antagonist diphenhydramine and the second-generation histamine H(1)- antagonist fexofenadine on seizure development of pentylenetetrazole (PTZ)-induced kindling in rats.</p><p><b>METHODS</b>The first-or second-generation histamine H(1)-antagonists and/or histidine were ip injected in rats every 48 h, followed by a subconvulsive dose of PTZ (35 mg/kg). Then the behavioral changes were observed for 30 min after every injection of PTZ. The histamine content of brain was measured spectrofluorometrically.</p><p><b>RESULT</b>Compared with the control group, diphenhydramine (5 mg/kg) significantly augmented the severity of seizure development of PTZ-induced kindling, whereas fexofenadine (5 mg/kg) had no marked influence. The effects of diphenhydramine were antagonized by histidine, the precursor of histamine.</p><p><b>CONCLUSION</b>Seizure development of PTZ-induced kindling is promoted by the first-but not the second generation histamine H(1)-antagonists via the blockade of brain histamine H(1)-receptor.</p>