Endomorphin 1 is a high affinity and selective agonist of the μ-opioid receptor and displays reasonable affinities for kappa3 binding sites (Ki: 20~30 nM).

Endomorphin is an endogenous opioid peptide and one of the two Endomorphins. It is a high affinity, a highly selective agonist of the μ-opioid receptor, and along with Endomorphin 2. Endomorphin 1 and Endomorphin 2 compete for both μ1 and μ2 receptor sites quite potently. Endomorphins have a little appreciable affinity for either delta or kappa1 binding sites, with Ki values greater than 500 nM.

Both Endomorphin 1 and Endomorphin 2 are potent analgesics with peak effects seen at 10 and 15 min, respectively. All subsequent studies are performed at peak effect. Both compounds are fully active supraspinally and spinally, with no indication of ceiling effects. Both Endomorphin 1 and Endomorphin 2 display a profile similar to morphine. Neither compound has analgesic activity in CXBK mice at a dose that produced over 70% analgesia in control CD-1 mice.

125I-Endomorphin 1 or 125I-Endomorphin 2 binding (0.2 nM) is performed in potassium phosphate buffer (50 mM, pH 7.4; 0.5 mL) with MgCl2 (5 mM) at a tissue concentration of 10 mg wet weight/mL for brains or 0.06 mg protein/mL for MOR-1/CHO cells. Specific binding is determined in the presence and absence of either 1 μM of the corresponding unlabeled peptide. The entire mixture is then incubated at 25°C for 1 hr and filtered over no. 32 glass fiber filters which have been presoaked for 1 hr in 0.5% polyethyleneimine and washed twice with ice-cold Tris buffer using a Brandel cell harvester. The filters are then counted on a Packard Cobra gamma counter. The other opioid receptor binding assays are performed.

Groups of mice are treated i.c.v. with Endomorphin 1 (12 μg) or Endomorphin 2 (3 μg) 15 min before a 0.5-cc charcoal meal (2.5% gum tragacanth,10% activated charcoal in water). The mice are killed 30 min later and the distance the charcoal traveled is measured.