[Effects between the first-and second-generation histamine H1-antagonists on seizure development of pentylenetetrazole-induced kindling in rats].
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.



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.



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.



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.
Jin
Chun-lei
CL
Department of Pharmacology, College of Medicine, Zhejiang University, Hangzhou 310031, China.
Chen
Zhong
Z
Zhang
Li-san
LS
Guo
Yi
Y
Zhang
Liu-yan
LY
Yanai
Kazuhiko
K
D000818:Animals; D006632:Histamine / Q000502:physiology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D039563:Histamine H1 Antagonists, Non-Sedating / Q000494:pharmacology*; D006639:Histidine / Q000494:pharmacology; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D010433:Pentylenetetrazole; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced*
D006634:Histamine H1 Antagonists; D039563:Histamine H1 Antagonists, Non-Sedating; D006639:Histidine; D006632:Histamine; D010433:Pentylenetetrazole