A growing body of literature has shown that kappa-opioid receptors are implicated in a variety of behavioral pain models. Several different classes of peripherally restricted peptidic and nonpeptidic kappa-opioid receptor agonists (KORAs) have been identified and show utility in treating painful conditions. The pharmacological profile of kappa-opioid receptor agonists in visceral pain models suggest that peripherally restricted KORAs are potentially useful for a variety of peripheral pain states.1


Moreover, peripherally restricted KORAs exhibit analgesic effects without activating reward pathways, thus reducing the risk of abuse and addiction associated with mu-opioids.2


Peripherally restricted kappa opioid agonists have been developed to target kappa opioid receptors located on visceral and somatic afferent nerves for relief of inflammatory, visceral, and neuropathic chronic pain. The recently shown efficacy of these analgesics—combined with a possible lower abuse potential and side effect burden than mu opioid receptor agonists—makes delta and peripherally restricted kappa opioid receptor agonists promising targets for treating pain.3

1 Kivell B, Prisinzano TE. Kappa opioids and the modulation of pain. Psychopharmacology (Berl) 2010 June;210(2):109-19.
2 Negri A, Rives ML, Caspers MJ, Prisinzano TE, Javitch JA, Filizola M. Discovery of a novel selective kappa-opioid receptor agonist using crystal structure-based virtual screening. J Chem Inf Model 2013 March 25;53(3):521-6.
3 Vanderah TW. Delta and kappa opioid receptors as suitable drug targets for pain. Clin J Pain 2010 January;26 Suppl 10:S10-S15