The nociceptin opioid peptide (NOP) receptor and its endogenous ligand nociceptin/orphanin FQ (N/OFQ) are the fourth members of the opioid receptor and opioid peptide families. Although they have considerable sequence homology to the other family members, they are not considered opioid per se because they do not have pharmacological profiles similar to the other family members. The number of NOP receptors in the brain is higher than the other family members, and NOP receptors can be found throughout the brain. Because of the widespread distribution of NOP receptors, N/OFQ and other peptide and small molecule agonists and antagonists have extensive CNS activities. Originally thought to be anti-opioid, NOP receptor agonists block some opioid activities, potentiate others, and modulate other activities not affected by traditional opiates. Because the effect of receptor activation can be dependent upon site of administration, state of the animal, and other variables, the study of NOP receptors has been fraught with contradictions and inconsistencies. In this article, the actions and controversies pertaining to NOP receptor activation and inhibition are discussed with respect to CNS disorders including pain (acute, chronic, and migraine), drug abuse, anxiety and depression. In addition, progress towards clinical use of NOP receptor-directed compounds is discussed.

伤害感受肽阿片肽 (NOP) 受体及其内源性配体伤害感受肽/孤啡肽 FQ (N/OFQ) 是阿片受体和阿片肽家族的第四个成员。尽管它们与其他家族成员具有相当大的序列同源性，但它们本身不被视为阿片类药物，因为它们不具有与其他家族成员相似的药理学特征。大脑中NOP受体的数量高于其他家族成员，并且NOP受体遍布整个大脑。由于NOP受体的广泛分布，N/OFQ和其他肽和小分子激动剂和拮抗剂具有广泛的CNS活性。 NOP 受体激动剂最初被认为是抗阿片类药物，它可以阻断某些阿片类药物的活性，增强其他药物的活性，并调节其他不受传统阿片类药物影响的活性。由于受体激活的效果可能取决于给药部位、动物状态和其他变量，因此 NOP 受体的研究充满了矛盾和不一致。在本文中，讨论了与中枢神经系统疾病有关的 NOP 受体激活和抑制的作用和争议，包括疼痛（急性、慢性和偏头痛）、药物滥用、焦虑和抑郁。此外，还讨论了 NOP 受体导向化合物的临床应用进展。