Nutt D, Lingford-Hughes A
Psychopharmacology Unit, University of Bristol, Bristol, UK.
Br J Pharmacol. 2008 May;154(2):397-405. doi: 10.1038/bjp.2008.101. Epub 2008 Apr 14.
This review gives an overview of what we see as the key issues in the human pharmacology of drugs of addiction. We review evidence of efficacy and mechanisms by which treatments act and point out areas where further work is needed. The role of agonist, partial agonist and antagonist treatments for opioid addiction is detailed and current issues relating to the mechanisms of actions at the receptor level and how to improve on compliance are discussed. The role of the brain dopamine and GABA-A systems in drug dependence is considered in relation to the growing pharmacology of these receptor systems, and the current status of novel preclinical targets reviewed. In addition, the different roles of dynamic and kinetic factors in both addiction and its treatment are discussed in relation to the underlying neuropharmacology of the disorders as defined from human and preclinical studies. Finally, some pointers to future research and especially to drug development by pharma are elaborated.
本综述概述了我们认为成瘾药物人体药理学中的关键问题。我们回顾了治疗方法起作用的疗效和机制证据,并指出了需要进一步研究的领域。详细阐述了激动剂、部分激动剂和拮抗剂治疗阿片类药物成瘾的作用,并讨论了当前在受体水平的作用机制以及如何提高依从性方面的问题。结合这些受体系统不断发展的药理学,探讨了脑多巴胺和GABA - A系统在药物依赖中的作用,并综述了新型临床前靶点的现状。此外,还结合从人体和临床前研究中确定的疾病潜在神经药理学,讨论了动态和动力学因素在成瘾及其治疗中的不同作用。最后,阐述了一些未来研究的方向,特别是制药行业药物开发的方向。