Normal electroretinogram and no toxicity signs after chronic and acute administration of the alcohol dehydrogenase inhibitor 4-methylpyrazole to the cynomolgus monkey (Macaca fascicularis)--a possible new treatment of methanol poisoning.
High doses of 4-methylpyrazole (4-MP) could be administered to monkeys in long- and short-term experiments without yielding any general toxicity or any toxic influence on the retinal photoreceptors, the conduction of impulses through the retina or on the activity in the inner nuclear layer detectable by recording the electroretinogram (ERG). Both series included a low dose (20 mg/kg) and a high dose level (100 mg/kg), the former being a tentative therapeutic dose. In the first series the substance was administered for 6 weeks and the toxicity regarding clinical signs, hematology and blood chemistry, and gross and microscopic pathology evaluated. Furthermore ophthalmoscopy with assessment of the fundus structures and recordings of the ERG were performed. The second series was mainly concerned with revealing of any direct effect of 4-MP on the ERG. Because of the low toxicity of 4-MP and its powerful inhibitory capacity on alcohol dehydrogenase, the substance should prove a potential tool in clinical alcohol research and an effective antidote in clinical situations where inhibition of alcohol dehydrogenase (ADH) is the key to a successful outcome of, for example, methanol and ethylene glycol poisoning.
D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D004596:Electroretinography; D000077604:Fomepizole; D008252:Macaca fascicularis; D008297:Male; D000432:Methanol / Q000506:poisoning*; D011720:Pyrazoles / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D012160:Retina / Q000502:physiology*; D013997:Time Factors
D011720:Pyrazoles; D000077604:Fomepizole; D000429:Alcohol Oxidoreductases; D000432:Methanol