mk-1064

Description: MK-1064 is a novel, potent, selective and orally bioavailable antagonist of Orexin OX2 Receptor, it has the potential to be used for the treatment of insomnia. Orexin neuropeptides regulate sleep/wake through orexin receptors (OX1R, OX2R); OX2R is the predominant mediator of arousal promotion. MK-1064 is an OX2R-single antagonist. Preclinically, MK-1064 promotes sleep and increases both rapid eye movement (REM) and non-REM (NREM) sleep in rats at OX2R occupancies higher than the range observed for dual orexin receptor antagonists. Similar to dual antagonists, MK-1064 increases NREM and REM sleep in dogs without inducing cataplexy. MK-1064 demonstrated dose-dependent increases in subjective somnolence (via Karolinska Sleepiness Scale and Visual Analogue Scale measures) and sleep (via polysomnography), including increased REM and NREM sleep.

References: ChemMedChem. 2014 Feb; 9(2):311-22; Sci Rep. 2016 Jun 3; 6:27147.