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Updated: Aug 24, 2026

Behavioral Characterization of Pentylenetetrazole-induced Seizures: Moving Beyond the Racine Scale
Published on: July 8, 2025
[Effects between the first-and second-generation histamine H1-antagonists on seizure development of
Chun-lei Jin1, Zhong Chen, Li-san Zhang
1Department of Pharmacology, College of Medicine, Zhejiang University, Hangzhou 310031, China.
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.
Result:
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.
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