Objective: 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. Methods: 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. Results: 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. Conclusion: 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.