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Effect of thioperamide, a histamine H3 receptor antagonist, on electrically induced convulsions in mice.

Abstract
The effect of thioperamide, a histamine H3 receptor antagonist, on electrically induced convulsions was studied in mice. Thioperamide significantly and dose dependently decreased the duration of each phase of convulsion and raised the electroconvulsive threshold. Its anticonvulsant effects were prevented by pretreatment with (R)-alpha-methylhistamine, a histamine H3 receptor agonist. These findings suggest that the effect of thioperamide on electrically induced convulsions is due to an increase in endogenous histamine release in the brain, an effect mediated by histamine H3 receptors. The anticonvulsant effect of thioperamide was antagonized strongly by mepyramine (or pyrilamine), a centrally acting histamine H1 receptor antagonist, but not by zolantidine, a centrally acting histamine H2 receptor antagonist. Thus, the blockade by mepyramine of the thioperamide-induced decrease in seizure susceptibility indicates that histamine released by thioperamide from the histaminergic nerve terminals interacts with the histamine H1 receptors of postsynaptic neurons. These findings support the hypothesis that the central histaminergic system is involved in the inhibition of seizures.
AuthorsH Yokoyama, K Onodera, K Iinuma, T Watanabe
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 234 Issue 1 Pg. 129-33 (Mar 30 1993) ISSN: 0014-2999 [Print] Netherlands
PMID8386092 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anticonvulsants
  • Histamine Antagonists
  • Piperidines
  • Receptors, Histamine
  • Receptors, Histamine H3
  • thioperamide
Topics
  • Animals
  • Anticonvulsants (pharmacology)
  • Electroshock
  • Histamine Antagonists
  • Male
  • Mice
  • Mice, Inbred Strains
  • Piperidines (pharmacology)
  • Receptors, Histamine (physiology)
  • Receptors, Histamine H3
  • Seizures (drug therapy, physiopathology)

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