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Table 1 Efficacy as measured by active wake reduction by suvorexant and DORA-12 relative to plasma exposure and OX 2 R exposure in rats

From: The duration of sleep promoting efficacy by dual orexin receptor antagonists is dependent upon receptor occupancy threshold

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***
  1. aOcc, occupancy.
  2. 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.
  3. cMean percent change in active wake relative to vehicle in the 2 h following treatment (**, ***, p < 0.01, 0.001, population t-test).