Category: receptor_pharmacology
Gi/o-coupled GPCRs activated by endogenous opioid peptides (β-endorphin, enkephalins, dynorphins) and exogenous opioid drugs. Downstream: Gi/o → adenylyl cyclase inhibition → reduced cAMP + PKA; Gβγ → opens K+ channels (hyperpolarization) + closes Ca2+ channels (reduces neurotransmitter release). MOR = analgesia + euphoria + respiratory depression + constipation + miosis (the canonical opioid effects). KOR = spinal analgesia + dysphoria + sedation + diuresis. DOR = mood + minor analgesia. β-arrestin recruitment vs G-protein activation underlies "biased agonism" — OLICERIDINE is a MOR G-protein-biased agonist with less β-arrestin recruitment, marketed claim of less respiratory depression per analgesic equivalent (clinical evidence modest). Mixed agonists/antagonists (NALBUPHINE κ + MOR-partial; BUPRENORPHINE MOR-partial) have a ceiling effect on respiratory depression. NALOXONE / naltrexone are antagonists at all three.