When mu-opioid related side effects are a concern in a peri-operative setting


Research has revealed that local application of exogenous opioid agonists produces a potent analgesic effect by activating peripheral opioid receptors in inflamed tissues. The analgesic activity occurs without activation of opioid receptors in the central nervous system (CNS), and therefore centrally mediated side effects, such as respiratory depression, mental clouding, altered consciousness, or addiction, are not associated with peripheral opioid activity. This discovery has stimulated research on developing peripherally restricted opioid agonists that lack CNS effects.1


Because a peripherally acting KORA does not activate receptors other than KORs and does not readily enter the central nervous system, it is expected to be a safer and better tolerated analgesic than opioid agonists, such as morphine, that predominantly activate mu opioid receptors.


In a Phase 2, single-center, randomized, double-blind, placebo-controlled, parallel-group study in patients undergoing bunionectomy surgery, patients treated with a peripherally acting KORA experienced significantly better analgesia (one-sided P≤0.05) and fewer treatment–related adverse events (AEs) of nausea and vomiting than placebo (P=0.028 and P=0.034, respectively). Mild transient facial tingling (paresthesia) and somnolence were reported in several patients treated with a peripherally acting KORA. But there were no reports of psychiatric AEs characteristic of centrally acting kappa opioids.

1 Vanderah TW. Delta and kappa opioid receptors as suitable drug targets for pain. Clin J Pain 2010 January;26 Suppl 10:S10-S15