Partial Opioid Agonists

The opioid receptors are G protein-coupled receptors for endogenous opioid peptides; the mu receptor binds beta-endorphin, endomorphin and enkephalin peptides as well as natural and synthetic opioids including morphine, fentanyl, methadone and buprenorphine, and agonist binding couples it predominantly to Gi and Go proteins, inhibiting adenylate cyclase and N-type and L-type calcium channels and activating inward rectifying potassium channels. A partial agonist produces less than the maximal response even when it occupies the receptors - the defining property is submaximal intrinsic efficacy, not affinity - so its effect reaches a ceiling as the dose rises and it competes with any full agonist present. The buprenorphine label documents both halves: sublingual buprenorphine produces typical opioid agonist effects which are limited by a ceiling effect, with agonist effects reaching a maximum across a dose range, and buprenorphine can precipitate withdrawal signs and symptoms in individuals physically dependent on full opioid agonists.