4-(1h-imidazol-4-ylmethyl)piperidine and Seizures

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.

Topics: Animals; Dose-Response Relationship, Drug; Drug Synergism; Histamine; Histamine Release; Histidine; Imidazoles; Injections, Intraventricular; Kindling, Neurologic; Male; Methylhistidines; Pentylenetetrazole; Piperidines; Pyrilamine; Rats; Rats, Sprague-Dawley; Seizures; Thiourea