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S-methyl-N,N-diethylthiolcarbamate: a disulfiram metabolite and potent rat liver mitochondrial low Km aldehyde dehydrogenase inhibitor.
Alcohol. 1990 Mar-Apr; 7(2):165-9.A

Abstract

S-methyl-N,N-diethylthiolcarbamate-methyl ester (DETC-Me), a proposed disulfiram metabolite, was investigated both in vivo and in vitro for its effectiveness as a liver mitochondrial low Km aldehyde dehydrogenase (L Km ALDH) inhibitor. Male Sprague-Dawley rats were treated intraperitoneally with DETC-Me, killed at various times and L Km ALDH determined. DETC-Me was found to be a more potent in vivo inhibitor of L Km ALDH than either disulfiram, diethyldithiocarbamate (DDTC) or diethyldithiocarbamate-methyl ester (DDTC-Me). The ID50 for DETC-Me, DDTC-Me and disulfiram was 6.5, 15.5 and 56.2 mg/kg, respectively. The ID50 for DDTC was similar to DDTC-Me. Maximal inhibition of L Km ALDH occurred 30 minutes after DETC-Me administration. DETC-Me was ineffective as an in vitro inhibitor. DETC-Me produced a marked disulfiram-ethanol reaction (DER) at one-quarter of the dose of disulfiram or DDTC. Plasma DETC-Me in rats was greater after DETC-Me administration than after DDTC-Me, DDTC or disulfiram. In conclusion, DETC-Me is proposed to be a metabolite of disulfiram, and may be the immediate precursor of the chemical species responsible for L Km ALDH inhibition.

Authors+Show Affiliations

Hart BW
Department of Pharmacology and Toxicology, University of Kansas, Lawrence 66045.
Yourick JJ
No affiliation info available
Faiman MD
No affiliation info available

MeSH

Aldehyde DehydrogenaseAnimalsDisulfiramDitiocarbFemaleKineticsMaleMitochondria, LiverRatsRats, Inbred Strains

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2158327

Citation

Hart, B W., et al. "S-methyl-N,N-diethylthiolcarbamate: a Disulfiram Metabolite and Potent Rat Liver Mitochondrial Low Km Aldehyde Dehydrogenase Inhibitor." Alcohol (Fayetteville, N.Y.), vol. 7, no. 2, 1990, pp. 165-9.
Hart BW, Yourick JJ, Faiman MD. S-methyl-N,N-diethylthiolcarbamate: a disulfiram metabolite and potent rat liver mitochondrial low Km aldehyde dehydrogenase inhibitor. Alcohol. 1990;7(2):165-9.
Hart, B. W., Yourick, J. J., & Faiman, M. D. (1990). S-methyl-N,N-diethylthiolcarbamate: a disulfiram metabolite and potent rat liver mitochondrial low Km aldehyde dehydrogenase inhibitor. Alcohol (Fayetteville, N.Y.), 7(2), 165-9.
Hart BW, Yourick JJ, Faiman MD. S-methyl-N,N-diethylthiolcarbamate: a Disulfiram Metabolite and Potent Rat Liver Mitochondrial Low Km Aldehyde Dehydrogenase Inhibitor. Alcohol. 1990 Mar-Apr;7(2):165-9. PubMed PMID: 2158327.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - S-methyl-N,N-diethylthiolcarbamate: a disulfiram metabolite and potent rat liver mitochondrial low Km aldehyde dehydrogenase inhibitor. AU - Hart,B W, AU - Yourick,J J, AU - Faiman,M D, PY - 1990/3/1/pubmed PY - 1990/3/1/medline PY - 1990/3/1/entrez SP - 165 EP - 9 JF - Alcohol (Fayetteville, N.Y.) JO - Alcohol VL - 7 IS - 2 N2 - S-methyl-N,N-diethylthiolcarbamate-methyl ester (DETC-Me), a proposed disulfiram metabolite, was investigated both in vivo and in vitro for its effectiveness as a liver mitochondrial low Km aldehyde dehydrogenase (L Km ALDH) inhibitor. Male Sprague-Dawley rats were treated intraperitoneally with DETC-Me, killed at various times and L Km ALDH determined. DETC-Me was found to be a more potent in vivo inhibitor of L Km ALDH than either disulfiram, diethyldithiocarbamate (DDTC) or diethyldithiocarbamate-methyl ester (DDTC-Me). The ID50 for DETC-Me, DDTC-Me and disulfiram was 6.5, 15.5 and 56.2 mg/kg, respectively. The ID50 for DDTC was similar to DDTC-Me. Maximal inhibition of L Km ALDH occurred 30 minutes after DETC-Me administration. DETC-Me was ineffective as an in vitro inhibitor. DETC-Me produced a marked disulfiram-ethanol reaction (DER) at one-quarter of the dose of disulfiram or DDTC. Plasma DETC-Me in rats was greater after DETC-Me administration than after DDTC-Me, DDTC or disulfiram. In conclusion, DETC-Me is proposed to be a metabolite of disulfiram, and may be the immediate precursor of the chemical species responsible for L Km ALDH inhibition. SN - 0741-8329 UR - https://www.unboundmedicine.com/medline/citation/2158327/S_methyl_NN_diethylthiolcarbamate:_a_disulfiram_metabolite_and_potent_rat_liver_mitochondrial_low_Km_aldehyde_dehydrogenase_inhibitor_ DB - PRIME DP - Unbound Medicine ER -