Table also improved in type 2 diabetic

Table 1: Suvorexant Animal Testing Data Species Strain Model and Test Effect Reference Rat Sprague-Dawley Sleep architecture studies, receptor occupancy measurements, pharmacokinetic parameters assessment Compound 3 (suvorexant) significantly increased REM and delta sleep with a corresponding decrease in active wake. Compound 3 achieved greater than 90% OX2R receptor occupancy in the rat sleep study. Compound 3 pharmacokinetic parameters showed to have a high clearance with good bioavailability and a rapid onset of action in rats. Oxidative metabolism was observed as primary mode of elimination.

(Cox et al., 2010) Rat Sprague-Dawley Receptor occupancy measurements, locomotor activity measurements, sleep architecture studies Suvorexant is a potent and selective antagonist of both OX1R and OX2R. Suvorexant significantly reduced locomotion in a dose dependent manner as compared to vehicle-treated rats. Significant dose proportional increases in NREM SWS I and II (10–25%) and REM sleep (27–48%) were observed with coincident reductions in active wake (?29% to ?79%) compared to vehicle. Sleep latency onset reduced by 24–41%.

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(Winrow et al., 2011) Canine Beagle (dog) Sleep architecture studies Suvorexant typically caused dogs to assume sleep postures and had an overall significant decrease in active wake (?26% to ?37%) with corresponding increases in SWS I (70–259%), SWS II (189–210%), and REM sleep (2–37%) compared to vehicle. Sleep latency onset significantly reduced by 35–63%. (Winrow et al., 2011) Non-human Primate Macaca mulatta (monkey) Sleep architecture studies NHP dosed with Suvorexant assumed a sleep posture and showed reductions of active wake (?8%) with concurrent increases in SWS I (55%), SWS II (42%), and REM sleep (53%).

Sleep latency was significantly reduced by 39% compared to vehicle. (Winrow et al., 2011) Mouse C57BL/6J         db/db mice as a model of type 2 diabetes with sleep disturbances. Sleep recordings and glucose regulation assessment Suvorexant exhibited the ability to increase REM and NREM sleep times and decrease the awake time in db/db mice. As a result of these improved sleep disturbances, glucose metabolism was also improved in type 2 diabetic mice as compared to vehicle.       (Tsuneki et al., 2016) Mouse C57Bl/6 Locomotor activity measurements, sleep architecture studies. Suvorexant used as a positive control.

Compound 26 and suvorexant had a significant effect in reducing mouse motility. Suvorexant induced a very strong increase in REM sleep, which accounted for much of the increase in total sleep time. Suvorexant also increased NREM sleep but to a lesser extent. Compound 26 primarily increased sleep by a strong effect on NREM sleep. (Betschart et al., 2013)  


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