Salvinorin A analogs and other kappa-opioid receptor compounds as treatments for cocaine abuse

Bronwyn M. Kivell, Amy W.M. Ewald, Thomas E. Prisinzano

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

50 Scopus citations

Abstract

Acute activation of kappa-opioid receptors produces anti-addictive effects by regulating dopamine levels in the brain. Unfortunately, classic kappa-opioid agonists have undesired side effects such as sedation, aversion, and depression, which restrict their clinical use. Salvinorin A (Sal A), a novel kappa-opioid receptor agonist extracted from the plant Salvia divinorum, has been identified as a potential therapy for drug abuse and addiction. Here, we review the preclinical effects of Sal A in comparison with traditional kappa-opioid agonists and several new analogs. Sal A retains the anti-addictive properties of traditional kappa-opioid receptor agonists with several improvements including reduced side effects. However, the rapid metabolism of Sal A makes it undesirable for clinical development. In an effort to improve the pharmacokinetics and tolerability of this compound, kappa-opioid receptor agonists based on the structure of Sal A have been synthesized. While work in this field is still in progress, several analogs with improved pharmacokinetic profiles have been shown to have anti-addictive effects. While in its infancy, it is clear that these compounds hold promise for the future development of anti-addictive therapeutics.

Original languageEnglish
Title of host publicationAdvances in Pharmacology
Pages481-511
Number of pages31
DOIs
StatePublished - 2014

Publication series

NameAdvances in Pharmacology
Volume69
ISSN (Print)1054-3589
ISSN (Electronic)1557-8925

Keywords

  • Addiction
  • Drug abuse
  • Kappa-opioid receptor
  • Salvia divinorum
  • Salvinorin A

ASJC Scopus subject areas

  • Pharmacology

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