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The NOP Receptor System in Neurological and Psychiatric Disorders: Discrepancies, Peculiarities and Clinical Progress in Developing Targeted Therapies

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Abstract

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.

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  1. Department of Biomedical Sciences, Charles E. Schmidt College of Medicine, Florida Atlantic University, 777 Glades Rd, Boca Raton, FL, 33431, USA

    Lawrence Toll, Andrea Cippitelli & Akihiko Ozawa

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  1. Lawrence Toll
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Correspondence to Lawrence Toll.

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Supported by NIH grant DA023281 to LT.

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Dr. Toll is a Founder and has stock in Phoenix PharmaLabs. The Drs. Cippitelli and Ozawa declare no conflict of interest.

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LT, AC, and AO participated in the writing of the manuscript. AC and AO conducted some of the experiments described in the manuscript.

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Toll, L., Cippitelli, A. & Ozawa, A. The NOP Receptor System in Neurological and Psychiatric Disorders: Discrepancies, Peculiarities and Clinical Progress in Developing Targeted Therapies. CNS Drugs 35, 591–607 (2021). https://doi.org/10.1007/s40263-021-00821-0

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