Effects of endogenous histamine on seizure development of pentylenetetrazole-induced kindling in rats.
This study was performed to investigate whether or not endogenous histamine can protect seizure development of pentylenetetrazole (PTZ)-induced kindling in rats. An intracerebroventricular (i.c.v.) injection with clobenpropit (5 and 10 microg), a representative H(3)-antagonist, significantly prolonged the onset of kindling and inhibited the seizure stages in a dose-dependent manner. Its action was significantly reversed by both immepip (2 microg, i.c.v.), an H(3)-agonist, and alpha-fluoromethylhistidine (alpha-FMH, 10 microg, i.c.v.), a selective histidine decarboxylase inhibitor. alpha-FMH (20 microg, i.c.v.) and pyrilamine (1 and 5 mg/kg i.p.), a classical H(1)-antagonist, markedly augmented the severity of seizure development of PTZ-induced kindling. Therefore, these results indicate that brain endogenous histamine plays a certain protective role on seizure development of PTZ-induced kindling in rats, and that its protective roles are mediated by H(1)-receptors.
Zhang
Li-San
LS
Department of Neurobiology and Pharmacology, School of Medicine, Zhejiang University, Hangzhou, China.
Chen
Zhong
Z
Huang
Yu-Wen
YW
Hu
Wei-Wei
WW
Wei
Er-Qing
EQ
Yanai
Kazuhiko
K
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006632:Histamine / Q000096:biosynthesis* / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D006639:Histidine / Q000494:pharmacology; D007093:Imidazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007696:Kindling, Neurologic / Q000187:drug effects; D008297:Male; D008762:Methylhistidines / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D010880:Piperidines / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced* / Q000517:prevention & control*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D007093:Imidazoles; D008762:Methylhistidines; D010880:Piperidines; C085755:4-(1H-imidazol-4-ylmethyl)piperidine; D006639:Histidine; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D013890:Thiourea; D011738:Pyrilamine; C086108:clobenpropit; D010433:Pentylenetetrazole