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.
AuthorsLi-San Zhang, Zhong Chen, Yu-Wen Huang, Wei-Wei Hu, Er-Qing Wei, Kazuhiko Yanai
JournalPharmacology (Pharmacology) Vol. 69 Issue 1 Pg. 27-32 (Sep 2003) ISSN: 0031-7012 [Print] Switzerland
PMID12886027 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2003 S. Karger AG, Basel
Chemical References
  • Imidazoles
  • Methylhistidines
  • Piperidines
  • clobenpropit
  • 4-(1H-imidazol-4-ylmethyl)piperidine
  • Histidine
  • alpha-fluoromethylhistidine
  • Histamine
  • Thiourea
  • Pyrilamine
  • Pentylenetetrazole
  • Animals
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Histamine (biosynthesis, pharmacology)
  • Histamine Release (drug effects)
  • Histidine (pharmacology)
  • Imidazoles (antagonists & inhibitors, pharmacology)
  • Injections, Intraventricular
  • Kindling, Neurologic (drug effects)
  • Male
  • Methylhistidines (pharmacology)
  • Pentylenetetrazole (adverse effects, antagonists & inhibitors)
  • Piperidines (pharmacology)
  • Pyrilamine (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Seizures (chemically induced, prevention & control)
  • Thiourea (analogs & derivatives, antagonists & inhibitors, pharmacology)

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