Effect of 4-(diethylamino)benzaldehyde on ethanol metabolism in mice

M. I E Mahmoud, James John Potter, O. M. Colvin, J. Hilton, Esteban Mezey

Research output: Contribution to journalArticle

Abstract

The compound 4-(diethylamino)benzaldehyde (DEAB) is a potent inhibitor of cytosolic (class 1) aldehyde dehydrogenase (ALDH) in vitro and can overcome cyclophosphamide resistance in murine leukemia cells characterized by their high content of ALDH. In this study, we examined the in vivo effect of DEAB in mice on ethanol metabolism and on antipyrine clearance as a measure of the microsomal mixed function oxidase activity. DEAB administered in doses of 50 and 100 mg/kg increased the blood acetaldehyde concentration and decreased the plasma acetate concentration in mice treated with ethanol. A pharmacokinetic approach demonstrated that DEAB in doses of 50 and 100 mg/kg inhibited the fraction of ethanol converted to acetate by 32.5 and 67.5%, respectively. This inhibition was comparable with that produced by disulfiram. DEAB produced optimal inhibition of ALDH 10-15 min after administration. DEAB did not change the half-life or the total clearance of antipyrine. We conclude that DEAB is a potent inhibitor of ALDH in vivo and has no effect on the mixed function oxidase activity as determined by antipyrine clearance.

Original languageEnglish (US)
Pages (from-to)1223-1227
Number of pages5
JournalAlcoholism: Clinical and Experimental Research
Volume17
Issue number6
StatePublished - 1993

Fingerprint

Metabolism
Ethanol
Antipyrine
Aldehyde Dehydrogenase
Mixed Function Oxygenases
Acetates
Disulfiram
Pharmacokinetics
Acetaldehyde
4-(diethylamino)benzaldehyde
Cyclophosphamide
Half-Life
Leukemia
Blood
Plasmas

Keywords

  • 4-(Diethylamino)benzaldehyde
  • Acetate
  • Aldehyde Dehydrogenase
  • Ethanol

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

Effect of 4-(diethylamino)benzaldehyde on ethanol metabolism in mice. / Mahmoud, M. I E; Potter, James John; Colvin, O. M.; Hilton, J.; Mezey, Esteban.

In: Alcoholism: Clinical and Experimental Research, Vol. 17, No. 6, 1993, p. 1223-1227.

Research output: Contribution to journalArticle

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AB - The compound 4-(diethylamino)benzaldehyde (DEAB) is a potent inhibitor of cytosolic (class 1) aldehyde dehydrogenase (ALDH) in vitro and can overcome cyclophosphamide resistance in murine leukemia cells characterized by their high content of ALDH. In this study, we examined the in vivo effect of DEAB in mice on ethanol metabolism and on antipyrine clearance as a measure of the microsomal mixed function oxidase activity. DEAB administered in doses of 50 and 100 mg/kg increased the blood acetaldehyde concentration and decreased the plasma acetate concentration in mice treated with ethanol. A pharmacokinetic approach demonstrated that DEAB in doses of 50 and 100 mg/kg inhibited the fraction of ethanol converted to acetate by 32.5 and 67.5%, respectively. This inhibition was comparable with that produced by disulfiram. DEAB produced optimal inhibition of ALDH 10-15 min after administration. DEAB did not change the half-life or the total clearance of antipyrine. We conclude that DEAB is a potent inhibitor of ALDH in vivo and has no effect on the mixed function oxidase activity as determined by antipyrine clearance.

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