Endomorphin-1 vs Leu-enkephalin

Head-to-head comparison of Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) — benefits, dosing, side effects, research data, and where to buy.

Research Score

PropertyEndomorphin-1Leu-enkephalin
CategoryPain ManagementPain Management
Full NameTyr-Pro-Trp-Phe-NH2Tyr-Gly-Gly-Phe-Leu
Molecular Weight610.71 Da555.63 Da
Half-LifeMinutes in plasma1-5 minutes in plasma
Amino Acids45
Typical Dose0.1-10 ug per animal0.1-5 ug per animal
RouteIntrathecal / subcutaneousIntrathecal / intracerebroventricular
Purity≥98%≥98%
Studies Count6001000
Research StatusPre-clinicalPre-clinical

Endomorphin-1 Benefits

  • mu-opioid selectivity
  • potent antinociception
  • endogenous peptide scaffold
  • useful for receptor-discovery studies

Leu-enkephalin Benefits

  • delta-opioid activity
  • endogenous analgesic model
  • receptor-selective pharmacology
  • nociception pathway research

Endomorphin-1 Dosing

Intrathecal 0.1-10 ug per animal|Subcutaneous 0.1-5 ug per animal|In vitro 0.1-100 nM

Leu-enkephalin Dosing

Intrathecal 0.1-5 ug per animal|Intracerebroventricular 0.1-2 ug per animal|In vitro 1-100 nM

Endomorphin-1 Side Effects

  • respiratory depression at high exposure
  • sedation
  • tolerance and dependence potential

Leu-enkephalin Side Effects

  • sedation
  • constipation-like opioid effects
  • very short plasma stability

Research Overview

Endomorphin-1

Endomorphin-1 is a key research peptide in studies of endogenous mu-opioid signaling and spinal analgesia. Like other peptide analgesics, its main translational hurdles are enzymatic instability, limited oral bioavailability, and delivery across barriers.

Leu-enkephalin

Leu-enkephalin is a standard tool in opioid receptor and pain-transmission research because it helps distinguish delta- from mu-preferring signaling. Its research value is high, but its clinical utility is limited by rapid enzymatic breakdown and delivery challenges.

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Common Stacking Partners

Endomorphin-1 stacks with:

gabapentinketamine

Leu-enkephalin stacks with:

gabapentinketamine
mu-opioidendogenous-peptideanalgesiapain-modulationopioid-peptideenkephalindelta-opioid