Histamine-3 receptor antagonists reduce superoxide anion generation and lipid peroxidation in rat brain homogenates

J Pharm Pharmacol. 2005 Jun;57(6):781-5. doi: 10.1211/0022357056064.

Abstract

Using a cyanide model to induce neurotoxic effects in rat brain homogenates, we examined the neuroprotective properties of three H3 antagonists, namely clobenpropit, thioperamide and impentamine, and compared them to aspirin, a known neuroprotective agent. Superoxide anion levels and malondialdehyde concentration were assessed using the nitroblue tetrazolium and lipid peroxidation assays. Clobenpropit and thioperamide significantly reduced superoxide anion generation and lipid peroxidation. Impentamine reduced lipid peroxidation at all concentrations used, but only reduced superoxide anion generation at a concentration of 1 mM. In the lipid peroxidation assay, all the drugs compared favourably to aspirin. This study demonstrates the potential of these agents to be neuroprotective by exerting antioxidant effects.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Aspirin / pharmacology
  • Brain / drug effects*
  • Brain / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Histamine Agonists / pharmacology*
  • Imidazoles / pharmacology
  • In Vitro Techniques
  • Lipid Peroxidation / drug effects*
  • Male
  • Malondialdehyde / antagonists & inhibitors
  • Neuroprotective Agents / pharmacology*
  • Neurotoxicity Syndromes / drug therapy*
  • Piperidines / pharmacology
  • Potassium Cyanide / adverse effects
  • Rats
  • Rats, Wistar
  • Receptors, Histamine H3 / drug effects
  • Superoxides / antagonists & inhibitors*
  • Thiourea / analogs & derivatives
  • Thiourea / pharmacology

Substances

  • Antioxidants
  • Histamine Agonists
  • Imidazoles
  • Neuroprotective Agents
  • Piperidines
  • Receptors, Histamine H3
  • impentamine
  • Superoxides
  • Malondialdehyde
  • Thiourea
  • thioperamide
  • Potassium Cyanide
  • Aspirin
  • clobenpropit