Aldehyde dehydrogenase, inhibitors

Drug Treatment of Chronic Alcoholism (Aldehyde Dehydrogenase Inhibitors)... 

Helander, A. Lindahl-Kiessling, K. (1991) Increased frequency of acetaldehyde-induced sister-chromatid exchanges in human lymphocytes treated with an aldehyde dehydrogenase inhibitor. Mutat. Res., 264, 103-107... 

Lindros. K.O. et at. (1995) Phenethyl isothiocyanate, a new dietary liver aldehyde dehydrogenase inhibitor. J. Pharmacol. Exp. Then. 275.79-83. 

Agents that can inhibit dopamine-P-hydroxylase include disulfiram, fusaric acid, phenylpropargylamine, FLA 63, FLA 57, LY 10853 and SKF 102698. These agents are of value in experimental investigations, but none Is used clinically for this purpose (though disulfiram is used to modify ethanol metabolism by a different mechanism see aldehyde DEHYDROGENASE INHIBITORS). 

Other classes include aldehyde dehydrogenase inhibitors aldose reductase inhibitors aminopeptidase inhibitors aromatase inhibitors carboxypeptidase inhibitors cyclooxygenase inhibitors dihydrofolate... 

ANTIMICROBIAL with ANTIBACTERIAL and ANTIPROTOZOAL actions. It widely used orally for a range of bacterial and protozoal infections. It acts as a potent aldehyde DEHYDROGENASE INHIBITOR, which can lead to Significant interactions with other drugs. It is also a diamine oxidase INHIBITOR. 

Isolation and structure of coprine, the in vivo aldehyde dehydrogenase inhibitor of Coprinus atramentarius, P. Lindberg, R. Bergman and B. Wickberg, J. Chem. Soc., Perkin Trans. 1, 1977, 684. 

Some of the alcohol and aldehyde dehydrogenase inhibitors are also inhibitors of P450 2E1, making interpretations of in vivo ethanol metabolism studies difficult. 4-Methylpyrazole is an excellent inhibitor - and probably one of the best choices for in vitro experiments at this time. 

Amino-l,2,4-triazole and diethyldithiocarba-mate are mechanism-based inactivators. The latter is of interest in that the oxidized form, disul-firam (Antabuse ), is an aldehyde dehydrogenase inhibitor used in patients in alcohol aversion therapy. Many of the early animal and human studies on interactions of ethanol and disulfiram with various chemicals can now be rationalized in the context of P450 2E1 (refs [668], [669]). 

Staub, R- E., Sparks. S. E, Quistad. G. B., and Casida, J. E. (1995). 5-methylation as a bioactivation mechanism for mono-and dithiticarbamate pesticides as aldehyde dehydrogenase inhibitors. Chem. Res. Toxicol 8, 1063-1069. 

Lindberg P, Bergman R, Wickbeig B. Isolatim and structure of coprine, the in vivo aldehyde dehydrogenase inhibitor in Coprinus atramentarius, syntheses of ccprine and related cyclo-propanone derivatives. J Soc (1977) (6) 684-91. 

Butyraldoxlme is unusual among aldehyde dehydrogenase inhibitors... 

The hallucinogenic beverage ayahuasca used in the culture of Amazonian tribes contains both the bioactive amine N,N-dimethyltryptamine (DMT) and monoamine oxidase inhibitors, the beta-carboline alkaloids (McKenna, 2004) (Fig. 2). The presence of the MAO inhibitor causes a profound increase in the oral bioavailability of the DMT and generates a prolonged hallucinogenic event, one well known to the Shamans in these communities (Riba et al, 2003). The soy isoflavone daidzin, previously considered to be an aldehyde dehydrogenase inhibitor (Keung et al., 1997), has been shown to inhibit monoamine oxidases (Rooke et al, 2000) and may alter dopamine-mediated events in susceptible tissues. 

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