Targeting peripheral κ-opioid receptors for the non-addictive treatment of pain

Abstract

Drug addiction to prescription μ-opioid agonists used in the setting of pain is a major public health threat, affecting millions of Americans. κ-opioid agonists (KOAs) may serve as a possible solution. KOAs have demonstrated indistinguishable analgesic activity relative to μ-opioid agonists in models of acute and chronic pain; however, conventional KOAs suffer from central nervous system (CNS)-mediated psychoactive side-effects. In this review, we discuss our efforts, as well as other's efforts, in developing peripherally restricted KOAs with retained or improved efficacy in rodent models of pain. Results indicate that our lead compound, JT09, acts as efficacious as morphine in alleviating peripheral pain, while failing to produce undesired CNS-mediated side-effects. In this review, we discuss our former results and future directions.