Opioid Receptor
A group of G-protein coupled receptors found throughout the nervous system that mediate pain perception, mood, and reward. There are three main types — mu, delta, and kappa — each with distinct effects. Difelikefalin is a selective kappa opioid receptor agonist that does not cross the blood-brain barrier.
Technical Context
Opioid receptors (mu/MOR, delta/DOR, kappa/KOR, and the related nociceptin/orphanin FQ receptor/NOP) are GPCRs found throughout the nervous system and periphery. Mu receptors mediate analgesia, euphoria, respiratory depression, and physical dependence — the effects of morphine and fentanyl. Delta receptors modulate pain and mood. Kappa receptors mediate analgesia, dysphoria, and antipruritic effects. Difelikefalin is a highly selective KOR agonist (>500-fold selectivity over MOR) designed to not cross the blood-brain barrier, providing peripheral antipruritic and analgesic effects without central euphoria, addiction potential, or respiratory depression. This peripherally restricted approach represents a significant pharmacological advancement.