DISULFIRAM METABOLISM--ALCOHOLISM TREATMENT CONCEPTS

将在大鼠体内研究双硫兰-乙醇-反应(DER)，以期 双硫仑及其代谢物的药代动力学关系 二乙基二硫代氨基甲酸酯和二乙基二硫代氨基甲酸甲酯 DER的药效学。要测量的生化参数包括 血浆二硫代氨基甲酸二乙酯、二乙基二硫代氨基甲酸酯 酯、CS2和二乙胺。血液中的乙醇和乙醛以及 线粒体中的脑和肝脏乙醛脱氢酶(低KM和高KM)， 将测定溶体、微体和上清液组分。 生理测量将包括心率、血压和 核心温度。使用药物作为药理工具，其作用 乙醛脱氢酶、多巴胺-β-羟基酶、乙醛和 将对DER中的乙醇进行评估。抗坏血酸-蛋白质结合 大鼠体内相互作用及其对DER的否定作用 与各种生化和生理参数的相关性将 被研究。DER的药效学也将被研究以 描述脑多巴胺和去甲肾上腺素受体的作用。 纳入的研究包括使用中央管理的 儿茶酚胺类神经毒素6-羟基多巴胺的相互作用 在生产DER的过程中，双硫胺和乙醇之间存在差异。

The disulfiram-ethanol-reaction (DER) will be studied in rats in order to correlate the pharmacokinetic aspects of disulfiram and its metabolites diethyldithiocarbamate and diethyldithiocarbamate-methyl ester with the pharmacodynamics of the DER. Biochemical parameters to be measured include plasma disulfiram, diethyldithiocarbamate, diethyldithiocarbamate-methyl ester, CS2 and diethylamine. Blood ethanol and acetaldehyde as well as brain and liver aldehyde dehydrogenase (low and high Km) in mitochondrial, lysomal, microsomal and supernatant fractions will be determined. Physiological measurements will include heart rate, blood pressure, and core temperature. Using drugs as pharmacological tools, the role of aldehyde dehydrogenase, dopamine-Beta-hydroxylase, acetaldehyde, and ethanol in the DER will be evaluated. Ascorbate-protein binding interactions in vivo in rats, its effect on negating the DER, and the correlation with the various biochemical and physiological parameters will be studied. The pharmacodynamics of the DER also will be investigated to delineate the role of brain dopamine and norepinephrine receptors. Included are studies employing the central administration of 6-hydroxydopamine, a catecholamine neurotoxin, to study the interaction between disulfiram and ethanol in producing the DER.