4‐Methylpyrazole as an Inhibitor of Ethanol Metabolism: Differential Metabolic and Central Nervous Effects

Abstract

Abstract: The properties of 4‐methylpyrazole (4‐MP) as an inhibitor of ethanol metabolism were investigated in rats. No effect was seen on enzymatic determination of ethanol. 4‐MP in doses of 0.0053–3.0 mmol/kg brought about a competitive inhibition of the metabolism of 32.6 mmol ethanol per kg body weight ranging from 20.8 to 80.5 %. A dose of 0.017 mmol 4‐MP per kg gave an inhibition of 50 %. By varying the interval between the administration of 4‐MP and ethanol from 15 min. to 48 hrs, it was found that the inhibitory effect disappeared after 12 hrs. The influence of 4‐MP on ethanol‐induced incoordination was measured by a modified tilting‐plane technique. The mean maximal impairment was significant in all conditions, when compared to the controls. For ethanol alone the mean maximal impairment was 11.9 %, for 4‐MP alone 7.2 % and for ethanol + 4‐MP 14.9 %, the effect lasting for 8 hrs. Thus, 4‐MP exerts significant central depressant effects per se , and produces an enhancement and a prolongation of ethanol‐induced effects on coordination in the rat.