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Pharmacological effects of diethylthiocarbamic acid methyl ester, the active metabolite of disulfiram?
Eur J Pharmacol. 1989 Aug 03; 166(3):419-25.EJ

Abstract

A recently discovered metabolite, diethylthiocarbamic acid methyl ester (Me-DTC), has been found in the plasma of man and rats in much higher concentrations than any other described metabolite after therapeutic doses of disulfiram. Me-DTC, in contrast to other disulfiram metabolites, is a potent inhibitor of liver aldehyde dehydrogenase (ALDH) in vitro. Like disulfiram, Me-DTC had a pronounced hypothermic effect in rats. This hypothermic effect and the augmented blood pressure response to ethanol challenge in rats developed rapidly with Me-DTC but were somewhat delayed with disulfiram. The blood pressure response outlasted the presence of Me-DTC in plasma (less than 24 h); a significant effect was found 48 h after pretreatment but not 72 h after a single dose. No effect was observed when ethanol was given 15 min before Me-DTC or disulfiram. These latter two observations are consistent with a function of Me-DTC as a suicide inhibitor of ALDH. Since Me-DTC has been reported to inhibit ALDH in vitro, even under anaerobic conditions, Me-DTC may be the active metabolite of disulfiram.

Authors+Show Affiliations

Petersen EN
Department of Pharmacology, A/S Dumex, Copenhagen S, Denmark.

MeSH

AnimalsBlood PressureBody TemperatureDisulfiramDitiocarbDose-Response Relationship, DrugEthanolHemodynamicsInjections, IntraperitonealMaleMiceRatsRats, Inbred StrainsThiocarbamates

Pub Type(s)

Journal Article

Language

eng

PubMed ID

2806369

Citation

Petersen, E N.. "Pharmacological Effects of Diethylthiocarbamic Acid Methyl Ester, the Active Metabolite of Disulfiram?" European Journal of Pharmacology, vol. 166, no. 3, 1989, pp. 419-25.
Petersen EN. Pharmacological effects of diethylthiocarbamic acid methyl ester, the active metabolite of disulfiram? Eur J Pharmacol. 1989;166(3):419-25.
Petersen, E. N. (1989). Pharmacological effects of diethylthiocarbamic acid methyl ester, the active metabolite of disulfiram? European Journal of Pharmacology, 166(3), 419-25.
Petersen EN. Pharmacological Effects of Diethylthiocarbamic Acid Methyl Ester, the Active Metabolite of Disulfiram. Eur J Pharmacol. 1989 Aug 3;166(3):419-25. PubMed PMID: 2806369.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacological effects of diethylthiocarbamic acid methyl ester, the active metabolite of disulfiram? A1 - Petersen,E N, PY - 1989/8/3/pubmed PY - 1989/8/3/medline PY - 1989/8/3/entrez SP - 419 EP - 25 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 166 IS - 3 N2 - A recently discovered metabolite, diethylthiocarbamic acid methyl ester (Me-DTC), has been found in the plasma of man and rats in much higher concentrations than any other described metabolite after therapeutic doses of disulfiram. Me-DTC, in contrast to other disulfiram metabolites, is a potent inhibitor of liver aldehyde dehydrogenase (ALDH) in vitro. Like disulfiram, Me-DTC had a pronounced hypothermic effect in rats. This hypothermic effect and the augmented blood pressure response to ethanol challenge in rats developed rapidly with Me-DTC but were somewhat delayed with disulfiram. The blood pressure response outlasted the presence of Me-DTC in plasma (less than 24 h); a significant effect was found 48 h after pretreatment but not 72 h after a single dose. No effect was observed when ethanol was given 15 min before Me-DTC or disulfiram. These latter two observations are consistent with a function of Me-DTC as a suicide inhibitor of ALDH. Since Me-DTC has been reported to inhibit ALDH in vitro, even under anaerobic conditions, Me-DTC may be the active metabolite of disulfiram. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/2806369/Pharmacological_effects_of_diethylthiocarbamic_acid_methyl_ester_the_active_metabolite_of_disulfiram DB - PRIME DP - Unbound Medicine ER -