Mitochondrial toxin 3-nitropropionic acid evokes seizures in mice

Eur J Pharmacol. 1998 Oct 16;359(1):55-8. doi: 10.1016/s0014-2999(98)00648-7.

Abstract

3-Nitropropionic acid, a potent inhibitor of succinate dehydrogenase which thus compromises cellular energy metabolism, evoked convulsions in mice in a dose-dependent manner. CD50 for clonic seizures was 158.5 (144.1-174.3) mg/kg. Tonic seizures were not observed. Broad-spectrum anticonvulsants, namely diazepam, phenobarbital and valproate, prevented the occurrence of 3-nitropropionic acid-induced seizures with ED50 of 4.9 (3.1-7.6), 33.1 (17.9-61.0) and 389.7 (351.2-432.3) mg/kg, respectively. Diphenylhydantoin-like drugs (diphenylhydantoin, and carbamazepine), anti-absence drugs (trimethadione and ethosuximide) and acetazolamide were ineffective. The characteristics of 3-nitropropionic acid-induced seizures resembled those of convulsions evoked by another mitochondrial toxin, aminooxyacetic acid.

MeSH terms

  • Animals
  • Anticonvulsants / therapeutic use
  • Dose-Response Relationship, Drug
  • Male
  • Mice
  • Mitochondria / drug effects*
  • Neurotoxins / pharmacology
  • Nitro Compounds
  • Propionates / pharmacology*
  • Seizures / chemically induced*
  • Seizures / drug therapy

Substances

  • Anticonvulsants
  • Neurotoxins
  • Nitro Compounds
  • Propionates
  • 3-nitropropionic acid