189388-22-5

Ki: 20-30 nM (kappa ₃ opioid receptor)

Endomorphin 1 (EM-1) is an endogenous opioid peptide and one of the two Endomorphins. It is a high affinity, highly selective agonist of the μ-opioid receptor, and along with Endomorphin 2 (EM-2). The two Endomorphins display reasonable affinities for kappa ₃ binding sites, with K _i values between 20 and 30 nM. Endomorphin 1 and Endomorphin 2 compete both μ ₁ and μ ₂ receptor sites quite potently. Endomorphins have little appreciable affinity for either delta or kappa ₁ binding sites, with K _i 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. Endomorphin 1 is significantly more potent spinally than supraspinally and, at the spinal level, it is significantly more potent than Endomorphin 2. The response of both agents are readily reversed by naloxone. β-FNA, a highly selective μ antagonist, effectively reverses the actions of both Endomorphins. Both Endomorphin 1 and Endomorphin 2 display a profile similar to morphine. Neither compound have analgesic activity in CXBK mice at a dose which produced over 70% analgesia in control CD-1 mice.