Endomorphin-1

Pain / Analgesia

Also known as: EM-1, Tyr-Pro-Trp-Phe-NH2, Endomorphin 1

Endogenous Opioid PeptidesResearch phase: Endogenous peptide (precursor unknown)Regulatory: Endogenous peptide. Not approved as a drug. Research into endomorphin analogs for pain with fewer side effects is ongoing.

Mechanism

Endomorphin-1 is the body's most selective natural painkiller for the mu-opioid receptor — the same receptor targeted by morphine. This 4-amino-acid peptide has the highest selectivity for mu-opioid receptors of any known endogenous opioid, making it the "endogenous morphine." Despite its discovery in 1997, its precursor gene remains unidentified, making it one of the great mysteries of opioid biology.

Technical detail

Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) is a tetrapeptide with exceptionally high affinity (Ki ~0.36 nM) and selectivity (4000-15000x) for mu-opioid receptors (MOR) over delta and kappa subtypes. MOR activation produces Gi/Go-mediated inhibition of adenylyl cyclase, activation of GIRK channels, and inhibition of N/P/Q-type Ca2+ channels in pain pathways (PAG, dorsal horn, thalamus). Unlike enkephalins and dynorphins, the precursor protein for endomorphins has not been identified — it may be synthesized by a non-ribosomal mechanism or from an undiscovered gene. Produces potent analgesia with potentially less respiratory depression and constipation than classical opioids.

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