Mechanism responsible for epileptogenic activity by first-generation H1-antagonists in rats.
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.
Kamei
C
C
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, 700-8530, Okayama, Japan. kamei@pheasant.pharm.okayama-u.ac.jp
Ohuchi
M
M
Sugimoto
Y
Y
Okuma
C
C
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects*; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006639:Histidine / Q000494:pharmacology; D008297:Male; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced*
D002800:Cholinesterase Inhibitors; D006634:Histamine H1 Antagonists; D006639:Histidine; D010830:Physostigmine