Pleiotropic Effects of Kappa Opioid Receptor-Related Ligands in Non-human Primates

Mei Chuan Ko, Stephen M. Husbands

Research output: Chapter or section in a book/report/conference proceedingChapter or section

3 Citations (SciVal)

Abstract

The kappa opioid receptor (KOR)-related ligands have been demonstrated in preclinical studies for several therapeutic potentials. This chapter highlights (1) how non-human primates (NHP) studies facilitate the research and development of ligands targeting the KOR, (2) effects of the endogenous opioid peptide, dynorphin A-(1-17), and its analogs in NHP, and (3) pleiotropic effects and therapeutic applications of KOR-related ligands. In particular, synthetic ligands targeting the KOR have been extensively studied in NHP in three therapeutic areas, i.e., the treatment for itch, pain, and substance use disorders. As the KORs are widely expressed in the peripheral and central nervous systems, pleiotropic effects of KOR-related ligands, such as discriminative stimulus effects, neuroendocrine effects (e.g., prolactin release and stimulation of hypothalamic-pituitary-adrenal axis), and diuresis, in NHP are discussed. Centrally acting KOR agonists are known to produce adverse effects including dysphoria, hallucination, and sedation. Nonetheless, with strategic advances in medicinal chemistry, three classes of KOR-related agonists, i.e., peripherally restricted KOR agonists, mixed KOR/mu opioid receptor partial agonists, and G protein-biased KOR agonists, warrant additional NHP studies to improve our understanding of their functional efficacy, selectivity, and tolerability. Pharmacological studies in NHP which carry high translational significance will facilitate future development of KOR-based medications.

Original languageEnglish
Title of host publicationHandbook of Experimental Pharmacology
PublisherSpringer Science and Business Media Deutschland GmbH
Pages435-452
Number of pages18
DOIs
Publication statusPublished - 2022

Publication series

NameHandbook of Experimental Pharmacology
Volume271
ISSN (Print)0171-2004
ISSN (Electronic)1865-0325

Bibliographical note

Funding Information:
Acknowledgments Funding by the US National Institutes of Health, National Institute on Drug Abuse (DA023281, DA044775, DA044450, and DA049580), and National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR069861) is gratefully acknowledged. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US federal agencies.

Publisher Copyright:
© 2020, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Keywords

  • Analgesics
  • Antipruritics
  • Drug abuse
  • Itch
  • Kappa opioid receptor
  • Macaque
  • Mu opioid receptor
  • Neuroendocrine function
  • Opioids
  • Pain
  • Spinal cord

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology, Toxicology and Pharmaceutics(all)

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