Pharmacology of Endorphins and Enkephalins

Introduction

• Endogenous opioid peptides (EOPs) — naturally-occurring peptide neurotransmitters/neuromodulators that bind opioid receptors with high affinity and whose actions are blocked by naloxone; together they form an endogenous opioid system modulating pain, mood, reward, neuroendocrine output and GI motility.
• Opiate vs opioid — opiate = morphine, codeine & related alkaloids of opium (Papaver somniferum); opioid = any agent binding the opioid-receptor orthosteric site — so the term includes the endogenous enkephalins, endorphins and dynorphins.
• Three classical families + 1 — β-endorphin (μ>δ), Met-/Leu-enkephalin (δ≥μ) and dynorphins (κ); a fourth non-classical peptide, nociceptin/orphanin-FQ, acts only at the NOP receptor and is not naloxone-reversible. Endomorphins are a candidate μ-selective family whose precursor has never been identified.
• Discovery & significance — Hughes & Kosterlitz isolated the enkephalins from brain in 1975; the system explains why exogenous opioids work and underlies placebo, stress and acupuncture analgesia, reward circuitry and opioid use disorder — making it a recurring MD-level exam theme.