Dynorphin
A class of endogenous opioid peptides that preferentially bind to kappa opioid receptors. Dynorphins are involved in pain modulation, stress responses, and mood regulation. The kappa opioid receptor targeted by difelikefalin is the same receptor system that endogenous dynorphins naturally activate.
Technical Context
Dynorphins are derived from the prodynorphin precursor and include dynorphin A (17 aa), dynorphin B (13 aa), and alpha-neoendorphin. They preferentially bind kappa opioid receptors (KOR) — the same receptors targeted by difelikefalin. Dynorphins are found in the hypothalamus (appetite regulation), hippocampus (memory), striatum (reward/aversion), spinal cord (pain modulation), and peripheral tissues. KOR activation by dynorphins produces analgesia, dysphoria (opposite of euphoria), and anti-reward effects, and modulates itch sensation. Difelikefalin mimics dynorphin's peripheral KOR effects while being excluded from central KOR effects by its inability to cross the blood-brain barrier, thereby avoiding dysphoria.