Studies on the effect of 4-methylpyrazole on methanol poisoning using the monkey as an animal model: with particular reference to the ocular toxicity.
Young cynomolgus monkeys (Macaca fascicularis) were chosen as a model to investigate the ocular toxicity in animals poisoned with methanol and treated with 4-methylpyrazole (4-MP). The metabolism of methanol in the monkey was investigated after administration of 4-MP. Plasma levels of methanol, formic acid, 4-MP and 4-hydroxy-MP (4-OH-MP) were determined. After intramuscular injection, 4-MP was rapidly absorbed and depressed the elimination rate of methanol as well as the accumulation of formate in the blood. The results show the same great individual variations in monkeys as in humans regarding the susceptibility to methanol poisoning. Administration of a single dose of 5 g/kg induces a serious intoxication in most monkeys, causing death to some of them. Two monkeys receiving a single dose of 6 g/kg of methanol developed a serious initial inebriation and were treated with 4-MP. These monkeys survived and showed no signs of toxicity on ocular examinations which included ophtalmoscopy and electroretinogram (ERG) recordings.
D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005123:Eye / Q000187:drug effects*; D000077604:Fomepizole; D008252:Macaca fascicularis; D008297:Male; D000432:Methanol / Q000378:metabolism / Q000506:poisoning*; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D014785:Vision, Ocular / Q000187:drug effects
D011720:Pyrazoles; D000077604:Fomepizole; D000429:Alcohol Oxidoreductases; D000432:Methanol