COCAINE AND HEROIN ANTAGONISTS

可卡因和海洛因拮抗剂

• 批准号: 2119071
• 负责人: SYDNEY ARCHER
• 金额: $ 23.2万
• 依托单位: RENSSELAER POLYTECHNIC INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-04-01 至 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2119071
• 关键词: behavior test; cocaine; dopamine antagonists; dopamine receptor; drug addiction antagonist; drug design /synthesis /production; drug interactions; drug screening /evaluation; laboratory rat; morphine; opioid receptor; receptor binding

A major objective of this proposal is to design and synthesize long-acting compounds in the morphine class which will bind selectively to mu receptors and act in vivo as selective mu antagonists and will abolish bar-pressing in rats which press for morphine and another group which presses for cocaine. Two compounds which have been synthesized act as specific long-acting (>24h) mu antagonists. In preliminary studies one of them reduced bar-pressing in non-physically dependent rats which were trained to press for morphine and reduced the rate of bar-pressing in rats dependent on cocaine. These compounds and some of their congeners will be studied further in the hope of developing a new modality for treating heroin and cocaine abuse in man. Newly synthesized compounds will first be studied in receptor binding assays. Selectivity and wash-resistance will be the criteria for further evaluation. In vivo studies in mice will furnish data concerning selectivity and duration of action. Compounds of interest will be studied in rats trained to press for morphine and cocaine. Pure morphine antagonists and agonist/antagonists will be examined. Since all compounds selected for further evaluation will have a strong antagonist component, it is anticipated the dependence liability will be minimal. Another major objective of this proposal is to design and synthesize long- acting selective D1 receptor antagonists with the aim of developing agents which will be useful in treating cocaine abuse. The new agents will be tested in dopamine receptor binding assays of the D1 and D2 type to determine selectivity and wash-resistance. Promising compounds will be tested in the cocaine-dependent colony of rats.

该提案的一个主要目标是设计和合成长效 吗啡类的化合物，它将选择性地结合到μ 受体并在体内作为选择性μ拮抗剂起作用， 在大鼠中按压吗啡，另一组大鼠 迫切需要可卡因。 已经合成的两种化合物作为 特异性长效（> 24小时）μ拮抗剂。 在初步研究中， 他们减少了非身体依赖大鼠的压杆， 训练大鼠按压吗啡，降低大鼠按压横杆的速度 依赖可卡因 这些化合物和它们的一些同类物将被 希望能开发出一种新的治疗方法 海洛因和可卡因滥用。 新合成的化合物将首先在受体结合方面进行研究 分析。选择性和耐洗性将是进一步的标准。 评价 小鼠体内研究将提供以下数据 选择性和作用持续时间。将研究感兴趣的化合物 在老鼠身上进行的实验。 纯吗啡 将检查拮抗剂和激动剂/拮抗剂。 由于所有化合物 选择用于进一步评价的将具有强拮抗剂组分， 预计依赖责任将是最小的。 该提案的另一个主要目标是设计和合成长- 以开发药物为目的的选择性D1受体拮抗剂 这将有助于治疗可卡因滥用。 新探员将 在D1和D2型多巴胺受体结合试验中测试， 确定选择性和耐洗性。有前途的化合物将是 在可卡因依赖的大鼠群体中进行了测试。