Effect of Carbetapentane or Melatonin on Cyanide-Induced Neurotoxicity in Mice

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Subcutaneous injection (s.c.) of potassium cyanide (8 or 9 mg/kg) caused tonic and clonic seizures in 80 to 95% of the treated mice. However, the incidence of seizures was significantly reduced by intracerebroventricular preinjection of carbetapentane (50 nmol/brain), an inhibitor of glutamate release, or by subcutaneous preinjection of melatonin (20 mg/kg), a potent free radical scavenger. Potassium cyanide (8 mg/kg, s.c.) increased lipid peroxidation in the brain of mice 2.6-fold. The lipid peroxidation was completely abolished when tonic and clonic seizures were prevented by preadministration of melatonin (20 mg/kg). Furthermore, mortality elicited by potassium cyanide (8 or 9 mg/kg, s.c.) was also reduced by pretreatment with carbetapentane or melatonin. These results suggest that free radical formation and an increase in the release of glutamate may contribute in part to the development of neurotoxicity induced by potassium cyanide in mice.
社団法人日本薬学会の論文
1996-12-31