Medication development for addictive disorders: The state of the science
Medication development for addictive disorders: The state of the science
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DOI：
10.1176/appi.ajp.162.8.1432
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发表时间：
2005-08-01
影响因子：
17.7
通讯作者：
Elkashef, A
中科院分区：
文献类型：
--
作者：
Vocci, FJ;Acri, J;Elkashef, A
1989年，国家药物滥用研究所（NIDA）建立了药物开发计划。该方案的重点是开发阿片剂和可卡因依赖性的药物疗法，最近还开发了甲基苯丙胺和大麻依赖性的药物疗法。该计划的主要目标是优化现有的治疗方法，并为医生和患者扩大治疗选择。这次审查将集中在以下药物滥用障碍的药物治疗的发展：阿片类药物，可卡因，甲基苯丙胺和大麻依赖。如果不加以治疗，阿片剂和兴奋剂依赖会造成严重的发病率和死亡率。例如，使用非法阿片类药物与丙型肝炎感染、艾滋病毒感染和其他医疗后果的风险增加有关。例如，在一个实施例中，吸毒过量NIDA药物开发计划与制药合作伙伴成功开发了醋酸左美沙酮、丁丙诺啡和丁丙诺啡/纳洛酮治疗阿片类药物依赖。此外，几种市售药物已显示出减少可卡因使用的希望。有趣的是，这些药物可能通过不同的神经化学机制起作用，这表明联合治疗可能是合理的下一步，可以进一步增加可卡因依赖患者的治疗收益。药物开发计划还确定了多种神经元机制，这些机制会因长期滥用药物而改变。神经科学的进步已经确定了条件提示，药物启动，压力诱导的药物摄入量增加，以及减少额叶抑制机制的变化，这些都可能导致成瘾的发展，维持和可能的复发。强调了调节这些机制的潜在药物。
In 1989, the National Institute on Drug Abuse ( NIDA) established its Medications Development Program. This program has concentrated on developing pharmacotherapies for opiate and cocaine dependence and, more recently, for methamphetamine and cannabis dependence. The major goals of this program are to optimize existing treatments and to expand treatment options for physicians and patients. This review will concentrate on the development of pharmacotherapies for the following substance abuse disorders: opiate, cocaine, methamphetamine, and cannabis dependence. Left untreated, opiate and stimulant dependence are responsible for significant morbidity and mortality. For example, use of illicit opiates is associated with an increased risk of hepatitis C infection, HIV infection, and other medical consequences, e. g., an overdose. The NIDA Medications Development Program has had success in developing, with pharmaceutical partners, levomethadyl acetate, buprenorphine, and buprenorphine/naloxone for opiate dependence. Moreover, several marketed medications have shown promise in reducing cocaine use. Of interest, these medications likely operate through diverse neurochemical mechanisms, suggesting that combination therapy may be a rational next step that could increase treatment gains further in cocaine-dependent patients. The Medications Development Program has also identified multiple neuronal mechanisms that are altered by chronic administration of drugs of abuse. Advances in neuroscience have identified changes in conditioned cueing, drug priming, stress-induced increases in drug intake, and reduced frontal inhibitory mechanisms as all being possible for the development of, maintenance of, and possible relapse to addiction. Potential medications that modulate these mechanisms are highlighted.