Department of Pharmaceutical Sciences, Concordia University Wisconsin, Mequon, WI, USA.
Neuropharmacology. 2019 Jun;151:195-207. doi: 10.1016/j.neuropharm.2019.03.006. Epub 2019 Mar 8.
Prolonged treatment of chronic severe pain with opioid analgesics is frought with problematic adverse effects including tolerance, dependence, and life-threatening respiratory depression. Though these effects are mediated predominately through preferential activation of μ opioid peptide (μOP) receptors, there is an emerging appreciation that actions at κOP and δOP receptors contribute to the observed pharmacologic and behavioral profile of μOP receptor agonists and may be targeted simultaneously to afford improved analgesic effects. Recent developments have also identified the related nociceptin opioid peptide (NOP) receptor as a key modulator of the effects of μOP receptor signaling. We review here the available literature describing OP neurotransmitter systems and highlight recent drug and probe design strategies.
长期使用阿片类镇痛药治疗慢性严重疼痛会带来一些问题，包括耐受性、依赖性和危及生命的呼吸抑制。尽管这些作用主要是通过优先激活μ阿片肽（μOP）受体来介导的，但人们越来越认识到，κOP 和 δOP 受体的作用也有助于观察到μOP 受体激动剂的药理和行为特征，并且可能同时靶向这些受体以提供更好的镇痛效果。最近的发展还确定了相关的痛敏素阿片肽（NOP）受体作为μOP 受体信号作用的关键调节剂。在这里，我们回顾了描述 OP 神经递质系统的现有文献，并强调了最近的药物和探针设计策略。
