title: Effects of clobenpropit on pentylenetetrazole-kindled seizures in rats.
abstract: The purpose of this study was to investigate whether or not clobenpropit, a selective and potent histamine H(3) receptor antagonist, can protect from pentylenetetrazole (35 mg/kg)-kindled seizures in rats. I.c.v. injection with clobenpropit (10 and 20 microg) significantly delayed the seizure stage and prolonged the latency to the onset of myoclonic jerks and the latency to the clonic generalized seizure in a dose-dependent manner. The protection by clobenpropit (20 microg) was completely antagonized by both immepip (5 and 10 microg, i.c.v.), a selective potent histamine H(3) receptor agonist, and alpha-fluoromethylhistidine (alpha-FMH, 50 microg, i.c.v.), a selective histidine decarboxylase inhibitor. In addition, clobenpropit markedly potentiated the histidine (100 and 200 mg/kg)-induced inhibition of pentylenetetrazole-kindled seizures. Pyrilamine (2 and 5 microg, i.c.v.) reversed the inhibition of pentylenetetrazole-kindled seizures induced by clobenpropit, whereas cimetidine had no effect even at a high dose of 5 microg. These results indicate that clobenpropit protects against pentylenetetrazole-kindled seizures in rats, and that its action is mainly due to the activation of endogenous histamine by blocking autoinhibitory presynaptic histamine H(3) receptors.
authors.affiliation: Department of Pharmacology and Neurobiology, School of Medicine, Zhejiang University, Hangzhou 310031, China.
authors.forename: Lisan
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
authors.forename: Keming
authors.initials: K
authors.lastname: Ren
authors.forename: Rob
authors.initials: R
authors.lastname: Leurs
authors.forename: Junchun
authors.initials: J
authors.lastname: Chen
authors.forename: Wenbin
authors.initials: W
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Ye
authors.forename: Erqing
authors.initials: E
authors.lastname: Wei
authors.forename: Henk
authors.initials: H
authors.lastname: Timmerman
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D010433:Pentylenetetrazole / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018100:Receptors, Histamine H3 / Q000502:physiology; D012640:Seizures / Q000139:chemically induced* / Q000517:prevention & control*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000627:therapeutic use*
chemical_list: D007093:Imidazoles; D018100:Receptors, Histamine H3; D013890:Thiourea; C086108:clobenpropit; D010433:Pentylenetetrazole