Biological Activity
LY2444296 is a brain-penetrant, orally active, short-acting, high-affinity, potent and selective K (kappa) opioid receptor (KOR) antagonist (human K/μ/δ Ki = 0.565/35.8/211 nM against diprenorphine binding; GTP-γ-S binding IC50/agonist/subtype transfectant = 1.57 nM/300 nM U69593/K, 21.3 nM/1 μM DAMGO/μ 293 nM/30 nM DPDPE/d). LY2444296 reverses K agonist antinociceptive efficacy in vivo (ED50 = 0.24 mg/kg p.o. against 1 mg/kg U69593 sc. by r at formalin test), decreases immobility time (10 or 30 mg/kg sc.) and prevents enhanced alcohol consumption (5 mg/kg i.p.) among mice subjected to stress by forced swimming.
