de Moura Fernando B, Kohut Stephen J, Bergman Jack
Behavioral Biology Program, McLean Hospital, Boston, MA, United States; Department of Psychiatry, Harvard Medical School, Boston, MA, United States.
Behavioral Biology Program, McLean Hospital, Boston, MA, United States; Department of Psychiatry, Harvard Medical School, Boston, MA, United States.
Adv Pharmacol. 2019;86:197-236. doi: 10.1016/bs.apha.2019.04.005. Epub 2019 Jun 3.
Despite decades of research, few medications have gained Food and Drug Administration (FDA) approval for the management of substance abuse disorder. The paucity of successful medications can be attributed, in part, to the lack of clearly identified neurobiological targets for addressing the core pathology of addictive behavior. Commonalities in the behavioral and brain processes involved in the rewarding effects of drugs and foods has prompted the evaluation of candidate medications that target neural pathways involved in both drug and eating disorders. Here, pharmacological strategies for the development of novel medications for drug addiction are presented in the context of potential overlapping neurobiological targets identified for eating disorders (e.g., obesity, overeating, binge-eating) and substance abuse. Mechanisms discussed in this chapter include modulators of the gut-brain axis (e.g., leptin, ghrelin, cholecystokinin, cocaine- and amphetamine-regulated transcript, and pancreatic peptides) and neurotransmitter systems (e.g., opioids, cannabinoids, dopamine, serotonin, and acetylcholine).
尽管经过了数十年的研究,但获得美国食品药品监督管理局(FDA)批准用于治疗物质使用障碍的药物却寥寥无几。成功药物的匮乏部分可归因于缺乏明确确定的神经生物学靶点来解决成瘾行为的核心病理问题。药物和食物奖励效应所涉及的行为和大脑过程中的共性促使人们对针对药物和饮食失调所涉及神经通路的候选药物进行评估。在此,在为饮食失调(如肥胖、暴饮暴食、暴食症)和物质滥用确定的潜在重叠神经生物学靶点的背景下,介绍了开发新型戒毒药物的药理学策略。本章讨论的机制包括肠脑轴调节剂(如瘦素、胃饥饿素、胆囊收缩素、可卡因和苯丙胺调节转录物以及胰肽)和神经递质系统(如阿片类物质、大麻素、多巴胺、5-羟色胺和乙酰胆碱)。