Table 1: Suvorexant Animal Testing Data

Species

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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%.

(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)