LONG ACTING ANTICOCAINE THEAPY

长效抗古卡因疗法

• 批准号: 6205126
• 负责人: HAROLD L KOMISKEY
• 金额: $ 5.71万
• 依托单位: XAVIER UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-14 至 2002-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6205126
• 关键词: abzyme; biotransformation; brain metabolism; cocaine; dopamine receptor; drug addiction antagonist; drug design /synthesis /production; laboratory rat; microcapsule; monoclonal antibody; pharmacokinetics; receptor binding

An epidemic of cocaine abuse has occurred in the United States. An alternative therapeutic approach for treating cocaine abuse, based on interrupting the distribution of cocaine to the dopamine neuronal uptake sites, is being developed. In this proposal an injectable microcapsule formulation containing a catalytic antibody to cocaine will be developed and evaluated for release characteristics in rodent in vivo experiments. More specifically, the usefulness of incorporating the catalytic antibody, Mab 15A10, within biodegradable microcapsules will be assessed by determining the area under the plasma concentration-time curve, plasma half-lives, and the volume of distribution after injections of different concentrations of Mab 15A10 in rodents. In addition, the effectiveness of Mab 15A10 released from biodegradable microcapsules will be assessed by measuring the formulation's ability to shift dose-response curves produced by acute and chronic daily injections of cocaine. Basically, the ability of various doses of acute and chronic daily injections of cocaine to alter locomotor activity, brain concentrations of dopamine and cocaine, and dopamine D2 and D1 receptor levels will be determined in the presence and absence of biodegradable microcapsules containing Mab 15A10.Dopamine D2 and D1 receptor will be measured in rodent basal ganglia, amygdala, and brain tissue anterior and medial to the caudate putamen using in vitro receptor binding assays.

美国出现了可卡因滥用的流行病。目前正在开发一种基于中断可卡因向多巴胺神经元摄取部位的分布的治疗可卡因滥用的替代治疗方法。在该提案中，将开发含有可卡因催化抗体的可注射微胶囊制剂，并在啮齿动物体内实验中评价其释放特性。更具体地，将催化性抗体Mab 15 A10掺入生物可降解微胶囊内的有用性将通过测定啮齿动物中注射不同浓度的Mab 15 A10后的血浆浓度-时间曲线下面积、血浆半衰期和分布体积来评估。此外，将通过测量制剂移动由可卡因的急性和慢性每日注射产生的剂量-反应曲线的能力来评估从可生物降解的微胶囊释放的Mab 15 A10的有效性。基本上，在存在和不存在含有Mab 15 A10的生物可降解微胶囊的情况下，测定各种剂量的可卡因的急性和慢性每日注射改变运动活性、多巴胺和可卡因的脑浓度以及多巴胺D2和D1受体水平的能力。以及尾壳核前部和中部的脑组织。