Proconvulsive effects of the mitochondrial respiratory chain inhibitor--3-nitropropionic acid

Eur J Pharmacol. 2000 Sep 8;403(3):229-33. doi: 10.1016/s0014-2999(00)00510-0.

Abstract

The role of impaired mitochondrial function in processes leading to the generation of seizures was studied in mice. An inhibitor of mitochondrial complex III, 3-nitropropionic acid, which is known to evoke convulsions per se, and was used here in subthreshold dose, enhanced seizures generated by electric current and application of 4-aminopyridine. In contrast, 3-nitropropionic acid did not affect convulsions induced by gamma-aminobutyric acid (GABA) receptor antagonists - bicuculline, pentylenetetrazol and picrotoxin, glycine antagonist - strychnine, cholinomimetic drug-pilocarpine, and kynurenine aminotransferase inhibitor - aminooxyacetic acid. It is hypothesised that deranged mitochondrial metabolism renders the central nervous system more susceptible to factors inducing seizures via direct depolarization.

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Convulsants / pharmacology*
  • Drug Interactions
  • Electric Stimulation
  • Electron Transport / drug effects*
  • Electroshock
  • Excitatory Amino Acid Antagonists / metabolism
  • Glycine / pharmacology
  • Kynurenic Acid / metabolism
  • Male
  • Mice
  • Nitro Compounds
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism
  • Propionates / pharmacology*
  • Seizures / chemically induced
  • Synaptic Transmission / drug effects
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Convulsants
  • Excitatory Amino Acid Antagonists
  • Nitro Compounds
  • Potassium Channels
  • Propionates
  • gamma-Aminobutyric Acid
  • Kynurenic Acid
  • Acetylcholine
  • 3-nitropropionic acid
  • Glycine