Mitochondrial toxin 3-nitropropionic acid evokes seizures in mice.
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.
Urbanska
E M
EM
Department of Pharmacology and Toxicology, Medical University School, Lublin, Poland. ewau@galen.imw.lublin.pl
Blaszczak
P
P
Saran
T
T
Kleinrok
Z
Z
Turski
W A
WA
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects*; D009498:Neurotoxins / Q000494:pharmacology; D009574:Nitro Compounds; D011422:Propionates / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy
D000927:Anticonvulsants; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; C015392:3-nitropropionic acid