Effects of 4-methylpyrazole, methanol/ethylene glycol antidote, in healthy humans

J Emerg Med. Jul-Aug 1990;8(4):455-61. doi: 10.1016/0736-4679(90)90176-v.


4-Methylpyrazole (4-MP), an inhibitor of alcohol dehydrogenase, may be useful for the treatment of methanol and ethylene glycol intoxications. A placebo-controlled, double blind, multiple dose, sequential, ascending-dose study has been performed to determine the tolerance of 4-MP in healthy volunteers. Oral loading doses of 4-MP were followed by supplemental doses every 12 h through 5 days, producing plasma levels in the therapeutic range. A slight, transient elevation in one or both serum transaminase values was observed in 6 of the 15 subjects treated with 4-MP. This effect was not dose related nor apparently mediated through a hypersensitivity reaction. Serum triglyceride levels were increased in 30% of 4-MP treated subjects, but also in 25% of the placebo subjects. 4-MP treatment did not produce any other significant changes in objective clinical parameters nor in subjective side effects. The results suggest that a mild, transient increase in liver function tests might be observed in some subjects treated with multiple doses of 4-MP. Nevertheless, the slower elimination rate and lesser degree of toxicity of 4-MP would make it preferable to ethanol in therapy of these poisonings.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Alcohol Dehydrogenase / antagonists & inhibitors
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Ethylene Glycols / metabolism
  • Ethylene Glycols / poisoning
  • Fomepizole
  • Humans
  • Male
  • Methanol / metabolism
  • Methanol / poisoning
  • Poisoning / drug therapy
  • Pyrazoles / administration & dosage
  • Pyrazoles / adverse effects*
  • Pyrazoles / therapeutic use


  • Ethylene Glycols
  • Pyrazoles
  • Fomepizole
  • Alcohol Dehydrogenase
  • Methanol