Selective kappa opioid receptor agonist could dial out side effects

In a study published in Cell, researchers at the University of North Carolina at Chapel Hill and colleagues solved the crystal structure of the kappa opioid receptor (KOR; OPRK1) bound to an opioid agonist and identified a compound that selectively activates KOR. The research identifies a potential structural "template" for KOR agonists that could treat pain with reduced side effects.

It has long been suspected that KOR activation could be useful for treating pain, addiction and affective disorders. Recently, two independent academic groups identified the receptor as a promising target for remyelinating axons in patients with multiple sclerosis. Despite extensive preclinical data implicating KOR as a disease target, its therapeutic potential has been limited by side effect liabilities such as dysphoria, sedation and hallucination, which are caused by induction of arrestin beta 2 (ARRB2) signaling downstream of KOR (see BioCentury Innovations, Sept. 15, 2016)...