Effect of Pyrazoles and Other Compounds on Alcohol Metabolism

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Abstract
Groups of 2 to 20 male Sprague Dawley rats (200-300 g) were injected intraperitoneally with possible alcohol-metabolism inhibitors, followed by 0.5 to 1.0 g of alcohol (7.5% w/v aqueous solution)/kg of body weight. Blood alcohol concentration was measured by analyzing by gas liquid chromatography the alcohol content of a 20- to 30-ml sample of air injected under the skin of the rat''s back. In doses of less than 0.5 mmole per kg the following compounds inhibited the rate of alcohol disappearance by 25% or more from a mean rate of 0.330 [plus or minus] 0.034 g per kg per hr: pyrazole, 4-brompyrazole, 4-methylpyrazole, 4-ethylpyrazole, 4-decylpyrazole, 4-carbethoxypyrazole, 4-[beta]-hydroxy-ethyl)pyrazole, 4-(gamma-hydroxypropyl)pyrazole, 4-(gamma-chloro-propyl)-pyrazole, 4-(gamma-aminopropyl)pyrazole, o-phenanthroline, and 2,2[image]-bipyridyL The following, in doses of 0.37 to 1.32 mmole/kg, did not inhibit alcohol disappearance: 3-methylpyrazole, 3,4-dimethyl-pyrazole, 3,5-dimethylpyrazole, 4-amyl-3-methylpyrazole, 1-methylol-3-undecylpyrazole, 3,5-pyrazoledicarboxylic acid, 3-methyl-2-pyra-zolin-5-one, antipyrine, 2,5-dimethylpyrrole, and 2-methylpyrazine; ic nor did 3.40 mmole of n-butyl alcohol, 11 mmole of methoxy- 1 ethanol/kg, 1 mmole of n-butoxyethanol, 40 mmole of dihydroxy-acetone or 60 mmole of propyelen glycol. The minimum lethal dose of pyrazole was about 18 mmole/kg. When the blood acetaldehyde concentration was increased to 40 mg/liter by giving 1.0 g of alcohol and 4 g of fructose/kg following 200 mg of calcium cyanamide/kg, administration of 1.5 mmole of pyrazole/kg decreased the acetaldehyde to an undetectable level in a few min. The possible uses of the inhibitors in the study of alcohol metabolism, as antidotes to alcohol-reaction producing substances and to control alcohol withdrawal symptoms are discussed.