LY2444296 is an orally bioavailable, high-affinity and selective short-acting kappa opioid receptor (KOPR) antagonist, with a Ki value of ∼1 nM. LY2444296 (3 mg/kg; i.p.; 30 min before U69,593 administration) prevents behavioral and neuroendocrine effects caused by the reference kappa agonist U69,593 in cocaine-naïve rats. LY2444296 reduces anxiety-like and depressive-like behaviors, as well as CORT release, in rats tested after chronic extended access cocaine self-administration, but not in cocaine-naïve rats[3]. LY2444296 [subcutaneous (s.c.) injection] at 10 and 30mg/kg, but not 3mg/kg, significantly decreased immobility time in a dose-dependent manner. LY2444296 and ADL5859 yielded significant synergistic effects for the antidepressant-like effect at the combined dose ranging from 3.84 mg/kg to 9.0 mg/kg[4]. κ(kappa)-selective doses of both LY2444296 (0.032-1 mg/kg) and LY2795050 (0.032-0.32 mg/kg) dose- and time-dependently prevented the grooming deficits caused by salvinorin A (1.8 m/kg)[5].
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