Endogenous morphine and its metabolites in mammals: History, synthesis, localization and perspectives

Morphine derived from Papaver somniferum is commonly used as an analgesic compound for pain relief. It is now accepted that endogenous morphine, structurally identical to vegetal morphine–alkaloid, is synthesized by mammalian cells from dopamine. Morphine binds mu opioid receptor and induces antinociceptive effects. However, the exact role of these compounds is a matter of debate although different links with infection, sepsis, inflammation, as well as major neurological pathologies (Parkinson’s disease, schizophrenia) have been proposed. The present review describes endogenous morphine and morphine derivative discovery, synthesis, localization and potential implications in physiological and pathological processes.

► Endogenous morphine and glucuronides are synthesized by mammalian cells from dopamine.
► Endogenous morphine-derived alkaloids are present in both GABA neurons and astrocytes.
► Endogenous morphine-derived alakaloid levels increase during stress, severe infections and some neurological diseases.