4-methylpyrazole decreases 1,4-butanediol toxicity by blocking its in vivo biotransformation to gamma-hydroxybutyric acid.

1,4-Butanediol (1,4-BD), a prodrug converted in vivo to gamma-hydroxybutyric acid by alcohol dehydrogenase, has resulted in life-threatening overdoses and deaths. We investigated whether 4-methylpyrazole (4-MP), an alcohol dehydrogenase antagonist, can be used as an antidote in a murine model of 1,4-BD overdose. CD-1 mice were overdosed with 1,4-BD, 600 mg/kg i.

Enzyme and receptor antagonists for preventing toxicity from the gamma-hydroxybutyric acid precursor 1,4-butanediol in CD-1 mice.

1,4-Butanediol (1,4-BD), the diol alcohol precursor of gamma-hydroxybutyric acid (GHB), undergoes in vivo enzymatic biotransformation to GHB by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase. The subsequent metabolite, GHB, is pharmacologically active at GABA(B) and GHB receptors. GHB can be metabolized in vivo to gamma-aminobutyric acid (GABA) and trans-4-hydroxycrotonic acid (T-HCA), which are also pharmacologically active at GABA(B) receptors and GHB receptors, respectively.