Related Experiment Videos
Mechanism responsible for epileptogenic activity by first-generation H1-antagonists in rats
C Kamei1, M Ohuchi, Y Sugimoto
1Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, 700-8530, Okayama, Japan. kamei@pheasant.pharm.okayama-u.ac.jp
Abstract:
In the present study, we have demonstrated that multiple first-generation H1-antagonists caused behavioral and EEG seizures in rats. The epileptogenic property of pyrilamine was more potent than either chlorpheniramine or diphenhydramine. In contrast, the second-generation H1-antagonists, loratadine and ebastine did not induce detectable epileptogenic activity. Intraperitoneal injection of histidine inhibited the EEG seizures induced by pyrilamine, diphenhydramine or chlorpheniramine; however no antagonism was observed with physostigmine. These results clearly suggest that the epileptogenic activity of first-generation H1-antagonists is dependent upon a centrally acting histaminergic mechanism.