Gerak Lisa R, Maguire David R, France Charles P
Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Addiction Research, Treatment and Training Center of Excellence, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Handb Exp Pharmacol. 2020;258:127-145. doi: 10.1007/164_2019_265.
Despite the therapeutic utility of opioids for relieving pain, other behavioral effects, including their potential for abuse and overdose, can be quite detrimental to individuals as well as society and have contributed to the ongoing opioid crisis. The dramatic escalation in overdose deaths over the last 15 years was initially driven by abuse of prescription opioids, although abuse of heroin, fentanyl, and fentanyl analogs has been increasing, largely due to increased availability and lower cost compared with prescription opioids. All of these opioids share pharmacological properties, acting as agonists at mu opioid receptors, and produce similar behavioral effects, including abuse-related, pain-relieving, dependence-producing, and respiratory-depressant effects. Despite their similarities, opioids are not pharmacologically identical. In fact, drugs that act at mu opioid receptors, including abused opioids, can vary on a number of dimensions, including pharmacological efficacy, drug-receptor interactions, receptor selectivity, and pharmacokinetics. Overall, these differences impact behavioral effects of drugs acting at mu opioid receptors, and this chapter describes variations in those behavioral effects and how these differences continue to provide new strategies that can be developed to address the ongoing opioid epidemic.
尽管阿片类药物在缓解疼痛方面具有治疗效用，但其其他行为效应，包括滥用和过量使用的可能性，对个人和社会都可能相当有害，并导致了持续的阿片类药物危机。过去15年中过量用药死亡人数的急剧上升最初是由处方阿片类药物的滥用驱动的，尽管海洛因、芬太尼和芬太尼类似物的滥用一直在增加，这主要是由于与处方阿片类药物相比，其可获得性增加且成本更低。所有这些阿片类药物都具有药理学特性，作为μ阿片受体的激动剂起作用，并产生类似的行为效应，包括与滥用相关的、止痛的、产生依赖性的和呼吸抑制作用。尽管它们有相似之处，但阿片类药物在药理学上并不完全相同。事实上，作用于μ阿片受体的药物，包括滥用的阿片类药物，在许多方面可能存在差异，包括药理效力、药物-受体相互作用、受体选择性和药代动力学。总体而言，这些差异会影响作用于μ阿片受体的药物的行为效应，本章将描述这些行为效应的变化，以及这些差异如何继续为应对持续的阿片类药物流行提供可开发的新策略。
