Leu-enkephalin vs Endomorphin-1

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

Research Score

PropertyLeu-enkephalinEndomorphin-1
CategoryPain ManagementPain Management
Full NameTyr-Gly-Gly-Phe-LeuTyr-Pro-Trp-Phe-NH2
Molecular Weight555.63 Da610.71 Da
Half-Life1-5 minutes in plasmaMinutes in plasma
Amino Acids54
Typical Dose0.1-5 ug per animal0.1-10 ug per animal
RouteIntrathecal / intracerebroventricularIntrathecal / subcutaneous
Purity≥98%≥98%
Studies Count1000600
Research StatusPre-clinicalPre-clinical

Leu-enkephalin Benefits

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

Endomorphin-1 Benefits

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

Leu-enkephalin Dosing

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

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 Side Effects

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

Endomorphin-1 Side Effects

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

Research Overview

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.

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.

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Common Stacking Partners

Leu-enkephalin stacks with:

gabapentinketamine

Endomorphin-1 stacks with:

gabapentinketamine
opioid-peptideenkephalindelta-opioidanalgesiamu-opioidendogenous-peptidepain-modulation