DISULFIRAM METABOLISM--ALCOHOLISM TREATMENT CONCEPTS

双硫仑代谢--酗酒治疗概念

• 批准号: 3108845
• 负责人: MORRIS David FAIMAN
• 金额: $ 7.44万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-09-01 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3108845
• 关键词: 6 hydroxydopamine; acetaldehyde; alcoholic beverage consumption; alcoholism /alcohol abuse therapy; aldehyde dehydrogenases; alpha antiadrenergic agent; apomorphine; beta antiadrenergic agent; brain metabolism; clonidine; desipramine; disulfiram; dopamine; dopamine beta monooxygenase; dopamine hydroxylase inhibitor; dosage; drug adverse effect; drug metabolism; ethanol; haloperidol; heart rate; high performance liquid chromatography; human age group; hypotension; hypothermia; liver metabolism; neural transmission; neurotoxins; norepinephrine; prazosin; propranolol; thiocarbamate; ultraviolet spectrometry; yohimbine

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.

将在大鼠中研究双硫仑-乙醇反应（DER），以 将双硫仑及其代谢物的药代动力学方面联系起来 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。 待测生化参数包括 血浆双硫仑，二乙基二硫代氨基甲酸酯，二乙基二硫代氨基甲酸甲酯 酯、CS2和二乙胺。 血液中的乙醇和乙醛 脑和肝线粒体中的醛脱氢酶（低和高Km）， 将测定溶酶体、微粒体和上清液部分。 生理测量将包括心率、血压和 核心温度 利用药物作为药理学工具， 醛脱氢酶，多巴胺-β-羟化酶，乙醛，和 将评估DER中的乙醇。 抗坏血酸-蛋白结合 在大鼠体内的相互作用，其对否定DER的作用，以及 与各种生化和生理参数的相关性将 被研究。 还将研究DER的药效学， 描述大脑多巴胺和去甲肾上腺素受体的作用。 包括使用以下药物的集中给药研究： 6-羟基多巴胺，一种儿茶酚胺类神经毒素，以研究 双硫仑和乙醇之间的关系