Suppression of Acetaldehyde Accumulation by 4-Methylpyrazole in Alcohol-Hypersensitive Japanese

Abstract

Abstract-Alcohol-sensitiveJapanese subjects with facial flushing and an increase in heart rate during ethanol intoxication exhibited marked individual variation in accumulation of acetaldehyde. This variation correlated well with the intensity of the above mentioned physiological responses.Oral pretreatment with 10 mg/kg 4-methylpyrazole, which inhibited the ethanol elimination rate by 15-25%, strongly suppressed both acetaldehyde accumulation and the associated responses. Under this condition, the sensitivity to acetaldehyde appeared to be reduced, and the correlation between the acetaldehyde level and the physiological responses disap peared.The effectiveness of even a low dose of 4-methylpyrazole suggests its clinical usefulness for alleviation of acute acetaldehyde toxicity in alcohol hypersensitive Japanese individuals as well as in disulfiram-treated alcoholics.

4‐Methylpyrazole Decreases Salivary Acetaldehyde Levels in ALDH2‐Deficient Subjects but Not in Subjects With Normal ALDH2

“…Even after a very small dose of alcohol, ALDH2-deficient subjects show marked cardiocirculatory stimulation with facial flushing, increased heart rate, and decreased blood pressure (Kupari et al, 1983). All these unpleasant physiologic effects as well as blood acetaldehyde levels were markedly suppressed in this study with the oral pretreatment with 4-MP, which is in accordance with earlier findings (Inoue et al, 1985). Furthermore, none of our volunteers reported any side effects from the medication with the dose used (10 -15 mg/kg body weight).…”

“…4-MP is used in clinical practice in the treatment of methanol and ethylene glycol poisonings (Jacobsen and McMartin, 1997). It is also known to be efficient in the management of the disulfiram-alcohol reaction and in reducing the flushing reaction and blood acetaldehyde level of ALDH2deficient subjects (Inoue et al, 1985;Lindros et al, 1981).…”