COCAINE AND HEROIN ANTAGONISTS

可卡因和海洛因拮抗剂

• 批准号: 3213499
• 负责人: SYDNEY ARCHER
• 金额: $ 10.63万
• 依托单位: RENSSELAER POLYTECHNIC INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-30 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3213499
• 关键词: 6,7 benzomorphan; buprenorphine; clinical depression; cocaine; drug abuse chemotherapy; drug addiction; drug addiction antagonist; drug design /synthesis /production; drug interactions; drug screening /evaluation; drug withdrawal; heroin; methadone; morphine; naloxone; naltrexone; narcotics; opioid receptor

The aims of this proposal are first, to develop a safe and effective cocaine antagonist, which when given to cocaine addicts, will abolish their craving for the drug and eliminate drug-seeking behavior. The second major aim of this proposal is to develop a heroin antagonist which can be used as a methodone replacement without the necessity of undergoing prior detoxification. These drugs should be long-acting, orally effective and have minimal or no abuse potential. Buprenorphine and naltrexone have been shown to decrease markedly cocaine abuse in human addicts (Kosten et al., Life Sci., 1989, 44, 887). Naltrexone, a pure opioid antagonist, will precipitate a severe withdrawal syndrome when given to heroin addicts, whereas buprenorphine, a mixed agonist-antagonist can be substituted for methadone, albeit with some discomfort to heroin addicts. Abrupt withdrawal from subjects maintained on 8 mg of buprenorphine produces a delayed but mild to moderate withdrawal syndrome for which the subjects demand drugs for relief. Since many cocaine addicts are heroin dependent, naltrexone is contraindicated in this population. We proposed to synthesize several examples in three chemically distinct groups of compounds which are putative mixed agonist-antagonists. These groups are: oripavines, 146-cinnamamidomorphinans and a new class of compounds, oxetanomorphinans. All target compounds will be tested at the medical college of Virginia and the Univ. of Michigan after submission to Dr. Arthur Jacobson (NIH).

该提案的目的是首先，开发一种安全有效的 可卡因拮抗剂，当给予可卡因成瘾者时， 他们对毒品的渴望和消除寻求毒品的行为。第二 该建议的主要目的是开发一种海洛因拮抗剂， 作为一种替代方法，无需事先进行 解毒这些药物应该是长效的，口服有效的， 具有最小或没有滥用潜力。 丁丙诺啡和纳洛酮已被证明可以显著减少可卡因 人类成瘾者的滥用（Kosten等人，生命科学，1989，44，887）。 纳洛酮是一种纯阿片类拮抗剂， 综合征时给予海洛因成瘾者，而丁丙诺啡，一种混合 激动剂-拮抗剂可以代替美沙酮，尽管一些 海洛因成瘾者的不适维持受试者突然退出 8毫克丁丙诺啡产生延迟但轻度至中度的 受试者需要药物缓解的戒断综合征。以来 许多可卡因成瘾者是海洛因依赖者，纳洛酮是禁忌的 在这个人群中 我们建议用三种不同的化学方法合成几个例子， 推定为混合激动剂-拮抗剂的化合物组。这些 组是：oripavines，146-cinnamamidomorphinans和一类新的 化合物，氧杂环丁烷吗啡。所有目标化合物将在 弗吉尼亚医学院和密歇根大学提交后， 博士亚瑟雅各布森（NIH）。