Methyl Diethyldithiocarbamate(Synonyms: S-甲基N,N二乙基二硫代氨基甲酸) 目录号 : GC49241
An active metabolite of disulfiram
Sample solution is provided at 25 µL, 10mM.
Methyl diethyldithiocarbamate is an active metabolite of the aldehyde dehydrogenase inhibitor disulfiram .1 It is produced by methylation of the disulfiram metabolite diethyldithiocarbamate in mouse liver microsomes.2 Methyl diethyldithiocarbamate inhibits liver low Km aldehyde dehydrogenase (ALDH) in rats (ID50 = 15.5 mg/kg).1 It decreases mean arterial pressure (MAP) and increases heart rate during ethanol challenge in rats when administered at a dose of 20.6 mg/kg.
1.Hart, B.W., Yourick, J.J., and Faiman, M.D.S-methyl-N,N-diethylthiolcarbamate: A disulfiram metabolite and potent rat liver mitochondrial low Km aldehyde dehydrogenase inhibitorAlcohol7(2)165-169(1990) 2.Gessner, T., and Jakubowski, M.Diethyldithiocarbamic acid methyl ester. A metabolite of disulfiramBiochem. Pharmacol.21(2)219-230(1972)
|溶解度||Chloroform: slightly soluble,Methanol: slightly soluble||储存条件||-20°C|
储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。
|1 mg||5 mg||10 mg|
|1 mM||6.1237 mL||30.6185 mL||61.237 mL|
|5 mM||1.2247 mL||6.1237 mL||12.2474 mL|
|10 mM||0.6124 mL||3.0618 mL||6.1237 mL|
|% DMSO % % Tween 80 % saline|
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
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Inhibition of aldehyde dehydrogenase by disulfiram and its metabolite methyl diethylthiocarbamoyl-sulfoxide
Biochem Pharmacol 1997 Feb 21;53(4):511-8.PMID:9105402DOI:10.1016/s0006-2952(96)00767-8.
Disulfiram (DSF) is presently the only available drug used in the aversion therapy of recovering alcoholics. It acts by inhibiting aldehyde dehydrogenase (ALDH), leading to high blood levels of acetaldehyde. The in vitro inhibition of ALDH by DSF and its metabolites was systematically studied by combined enzyme inhibition assay with direct molecular weight determination of the same sample using electrospray ionization-mass spectrometry (ESI-MS). Enzyme activity was measured after incubating yeast ALDH (yALDH) with excess concentrations of DSF, Methyl Diethyldithiocarbamate (MeDDC) and methyl diethylthiocarbamoyl-sulfoxide (MeDTC-SO) and then subjected to analysis by ESI-MS. Addition of DSF resulted in complete enzyme inhibition; however, ESI-MS analysis demonstrated no discernible shift in molecular weight, indicating that no intermolecular adduct was formed with the protein. Treatment of yALDH with MeDTC-SO also completely abolished yALDH activity with a concomitant increase of + approximately 100 Da in the molecular mass of the enzyme. This indicated formation of a covalent carbamoyl protein adduct. Furthermore, the effects of dithiothreitol (DTT) were examined on samples of inhibited protein in vitro. At pH 7.5, DTT completely reversed inhibition after DSF treatment. yALDH inhibited by MeDTC-SO could not be recovered by DTT at pH 7.5, but at pH 9 the enzymic activity was fully restored and a mass loss of approximately 100 Da was noted. This observations are consistent with mechanisms where inhibition of yALDH by DSF in vitro involves oxidation of the active site, whereas MeDTC-SO forms a covalent adduct with the protein in vitro resulting in cessation of enzyme activity.
Effect of thiocarbonyl compounds on alpha-naphthylisothiocyanate-induced hepatotoxicity and the urinary excretion of [35S]alpha-naphthylisothiocyanate in the rat
Toxicol Appl Pharmacol 1984 Mar 15;72(3):504-12.PMID:6324415DOI:10.1016/0041-008x(84)90127-3.
The effect of disulfiram (DSF), sodium diethyldithiocarbamate (DDTC), Methyl Diethyldithiocarbamate (Me-DDTC), and ethionamide on the hepatotoxic response of alpha-naphthylisothiocyanate (ANIT) was studied in the rat. The hyperbilirubinemic response of ANIT was significantly inhibited by ip or po DSF pretreatment. A more marked inhibition of toxicity occurred when DSF was given via ip injection. DDTC, Me-DDTC, and ethionamide significantly inhibited ANIT-induced hyperbilirubinemia. Me-DDTC is approximately three times more potent than DDTC as an inhibitor of toxicity. Approximately 16% of a dose of [35S]ANIT was excreted in the urine as inorganic sulfate 48 hr after dosing. Me-DDTC administered simultaneously with [35S]ANIT significantly reduced urinary [35S]sulfate excretion in the first 24 hr. Ethionamide reduced urinary [35S]sulfate excretion. Pretreatment with phenobarbital which stimulates toxicity in vivo increased urinary [35S]sulfate excretion 300% in the first 12 hr. Thus, this study shows that agents which sensitize or protect rats from the toxic effects of ANIT, correspondingly stimulate or inhibit the oxidative desulfuration of [35S]ANIT in vivo.