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Effects of NOP-Related Ligands in Nonhuman Primates

  • Norikazu Kiguchi
  • Mei-Chuan KoEmail author
Chapter
Part of the Handbook of Experimental Pharmacology book series

Abstract

The nociceptin/orphanin FQ peptide (NOP) receptor-related ligands have been demonstrated in preclinical studies for several therapeutic applications. This article highlights (1) how nonhuman primates (NHP) were used to facilitate the development and application of positron emission tomography tracers in humans; (2) effects of an endogenous NOP ligand, nociceptin/orphanin FQ, and its interaction with mu opioid peptide (MOP) receptor agonists; and (3) promising functional profiles of NOP-related agonists in NHP as analgesics and treatment for substance use disorders. NHP models offer the most phylogenetically appropriate evaluation of opioid and non-opioid receptor functions and drug effects. Based on preclinical and clinical data of ligands with mixed NOP/MOP receptor agonist activity, several factors including their intrinsic efficacies for activating NOP versus MOP receptors and different study endpoints in NHP could contribute to different pharmacological profiles. Ample evidence from NHP studies indicates that bifunctional NOP/MOP receptor agonists have opened an exciting avenue for developing safe, effective medications with fewer side effects for treating pain and drug addiction. In particular, bifunctional NOP/MOP partial agonists hold a great potential as (1) effective spinal analgesics without itch side effects; (2) safe, nonaddictive analgesics without opioid side effects such as respiratory depression; and (3) effective medications for substance use disorders.

Keywords

Analgesics Bifunctional ligands Chronic pain Drug abuse Inflammatory pain MOP receptor NOP receptor Opioids Parkinson’s disease Primate Spinal cord 

Notes

Acknowledgments

The US National Institutes of Health, National Institute on Drug Abuse (DA032568, DA035359, DA040104, and DA044775), National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR059193 and AR064456), and the US Department of Defense (W81XWH-13-2-0045) supported part of findings described in this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US federal agencies.

Conflict of Interest

N.K. and M.C.K. declare that there is no conflict of interest.

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of PharmacologyWakayama Medical UniversityWakayamaJapan
  2. 2.Department of Physiology and PharmacologyWake Forest School of MedicineWinston-SalemUSA

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