Compound
|
Dose (mg/kg)
|
Plasma (nM)
|
OX2R Occa(% maxb)
|
Active wake reductionc%
|
---|
Suvorexant
|
10
|
1600.0
|
92.6
|
-29.0***
|
|
30
|
2100.0
|
94.3
|
-79.6**
|
|
100
|
5100.0
|
97.6
|
-79.9**
|
DORA-12
|
0.3
|
20.2
|
34.0
|
-7.9
|
|
1
|
67.4
|
62.8
|
-9.7
|
|
3
|
202.2
|
83.0
|
-28.8***
|
|
10
|
674.0
|
93.9
|
-44.2***
|
|
30
|
2022.0
|
97.1
|
-45.9***
|
- aOcc, occupancy.
- bNormalized occupancy was determined over a range of doses and fit to a one-sided binding hyperbolic curve to determine the maximum occupancy. OX2R occupancies corresponding to plasma values at indicated doses were calculated based on the normalized curve for each compound.
- cMean percent change in active wake relative to vehicle in the 2 h following treatment (**, ***, p < 0.01, 0.001, population t-test).