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

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.

• Authors: G Haberek, T Tomczyk, B Zuchora, M Wielosz, W A Turski, E M Urbanska
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 403 Issue 3 Pg. 229-33 (Sep 08 2000) ISSN: 0014-2999 [Print] Netherlands
• PMID: 10973624 (Publication Type: Journal Article)

Chemical References

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

Topics

• 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, metabolism)
• Propionates (pharmacology)
• Seizures (chemically induced)
• Synaptic Transmission (drug effects)
• gamma-Aminobutyric Acid (pharmacology)