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Endogenous opioid tetrapeptide

Endomorphin-1

Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) is an endogenous opioid tetrapeptide and one of the most selective natural agonists of the mu-opioid receptor.

By The Peptides Codex Editorial TeamIndividual review date not recorded

Page data last changed: . Chemistry registry snapshot: . Registry refreshes and identity assessments are separate from scientific content review.

Length
4 aa
Class
Endogenous opioid tetrapeptide
Function
High-affinity, highly selective agonist of the mu-opioid receptor
Context
Endogenous neuropeptide and research tool in opioid pharmacology; not a Health Canada-authorized product

Among the most selective natural mu-opioid agonists known — proposed as an endogenous ligand of the receptor.

Also known as: EM-1

Part of the Neuropeptides & signaling cluster

Overview

Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) is an endogenous opioid tetrapeptide and one of the most selective natural agonists of the mu-opioid receptor. First described in 1997, it is widely used as a research tool in opioid pharmacology. This page is educational and makes no claim about pain relief or therapeutic use.

Source & context

Biological / chemical source: Mammalian central nervous system (endogenous)

Primary research or clinical context: Endogenous neuropeptide and research tool in opioid pharmacology; not a Health Canada-authorized product

Structure and selectivity

Endomorphin-1 is a C-terminally amidated tetrapeptide, Tyr-Pro-Trp-Phe-NH2, that binds the mu-opioid receptor with high affinity and unusually high selectivity over delta and kappa receptors. Along with endomorphin-2 it has been proposed as a genuine endogenous ligand of the mu receptor, and it is more prevalent in the brain than in the spinal cord.

Research role and limits

As a selective mu agonist, endomorphin-1 is a common probe in laboratory studies of opioid signalling and analgesia in animal models. Native peptides like this are quickly degraded and do not cross the blood-brain barrier well, which is why they remain research tools rather than medicines. This page is educational and does not describe a treatment.

Structure & chemistry

Molecular identity & reference confidence

Source-supported reference

The four-residue chains agree. -NH2 records the C-terminal amide described in the IUPHAR snapshot and PubChem structure. Bare sequence arithmetic omits that modification.

Molecular form
Endomorphin-1, amidated tetrapeptide
Species
Not established by this molecular identity audit
Termini (N / C)
Not specified / Amide

Average reference mass · Molecular identity assessment: 2026-10-05

Reference policy updated: 2026-10-05

Molecular formula
C34H38N6O5
Average reference mass
≈ 610.7
C-terminus
Amide
Identifiers

Chemistry values: PubChem, IUPHAR/BPS Guide to Pharmacology · fetched 2026-10-01.

Concentration math

Endomorphin-1 — reconstitution calculator

Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.

Reference form: Endomorphin-1, amidated tetrapeptideAverage reference mass: 610.7 Da

Syringe graduation
Solution concentration
5 mg/mL5,000 mcg/mL
mcg

Enter an amount to see the volume it corresponds to.

Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.

Open the Endomorphin-1 calculator on its own page →

FAQ about Endomorphin-1

What is Endomorphin-1?+

Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) is an endogenous opioid tetrapeptide and one of the most selective natural agonists of the mu-opioid receptor. First described in 1997, it is widely used as a research tool in opioid pharmacology. This page is educational and makes no claim about pain relief or therapeutic use.

What Canadian product status is recorded for Endomorphin-1?+

Canadian product status for Endomorphin-1 has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.

What is the typical length of Endomorphin-1?+

Endomorphin-1 is commonly described as approximately 4 amino acids (Endogenous opioid tetrapeptide).

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Obestatin
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Albiglutide
Incretin mimetic (GLP-1 receptor agonist)
Albiglutide is a GLP-1 receptor agonist created by genetically fusing two modified GLP-1 sequences to human serum albumin, giving it a long half-life suited to once-weekly dosing. Approved as Tanzeum and Eperzan in 2014, it was later withdrawn from the market for commercial reasons and is now a historical case study.
Neurotensin
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References & further reading

  1. 1.Tseng (2002). The antinociceptive properties of endomorphin-1 and endomorphin-2 in the mouse. Jpn J Pharmacol
  2. 2.Narita et al. (2002). Endomorphin-induced motivational effect: differential mechanism of endomorphin-1 and endomorphin-2. Jpn J Pharmacol
  3. 3.Fujita et al. (2006). Inhibition by endomorphin-1 and endomorphin-2 of excitatory transmission in adult rat substantia gelatinosa neurons. Neuroscience
  4. 4.Sakurada et al. (2002). Differential antinociceptive effects induced by intrathecally-administered endomorphin-1 and endomorphin-2 in mice. Jpn J Pharmacol
  5. 5.Sato et al. (2024). Distribution and anti-nociceptive function of endomorphin-1 in the rat cranial sensory ganglia. Biomed Res
  6. 6.Li et al. (2001). Analgesic effect of endomorphin-1. Acta Pharmacol Sin
  7. 7.Wu et al. (2017). Original endomorphin-1 analogues exhibit good analgesic effects. Bioorg Med Chem Lett
  8. 8.Horvath et al. (2003). Evaluation of endomorphin-1 on the activity of Na(+),K(+)-ATPase using in vitro and in vivo studies. Eur J Pharmacol
  9. 9.PubMed — Endomorphins and related opioid peptides (review, 12481550)
  10. 10.Wikipedia — Endomorphin-1
Disclaimer: Educational content only. Not medical advice. Not instructions for human use. Research peptides and unapproved products may be restricted or illegal to market for human consumption in your jurisdiction. Consult qualified professionals and applicable law.
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