Figure 3: MK-1064 requires higher OX2R occupancies to promote sleep relative to DORA-12 in rats.
From: Orexin 2 Receptor Antagonism is Sufficient to Promote NREM and REM Sleep from Mouse to Man
The mean percentage change (±SEM) in (a) active wake, (b) SWS, and (c) REM sleep in response to MK-1064 (at 0.3, 1, 5, 10 and 20 mg/kg) and DORA-12 (at 0.3, 1, 3, 10 and 30 mg/kg) calculated from PSG recordings versus the percentage OX2R occupancy determined in rats. Occupancy versus plasma exposure curves were determined and the exposure in satellite animals evaluated in parallel with PSG animals was used to determine corresponding OX2R occupancies at Cmax (1 hour) following treatment. Occupancies at which significant % change in active wake, SWS and REM sleep were observed over the 2 hours following treatment relative to vehicle are indicated (*, **, ***p < 0.05, 0.01, 0.001 respectively; one sample t-test for repeated measures).
