Diazepam and eszopiclone, but not DORA-22, exhibit next-day effects impacting cognitive performance in monkeys. Monkeys were treated (arrow) with sleep-promoting doses 2 h before the 12-h dark/inactive phase (gray shading): diazepam, 10 mg/kg, p.o. in 0.5% methylcellulose; eszopiclone, 10 mg/kg, in 20% Vitamin E TPGS; DORA-22, 30 mg/kg, in 20% Vitamin E TPGS. Memory and attention were evaluated by DMS (D) and SCRT (C) tasks 14 and 16 h after dosing, respectively. A. Time course of plasma levels after dosing (0, 0.25, 0.5, 1, 2, 4, 6, 17 h; n = 2, diazepam and eszopiclone; n = 3, DORA-22 [17 h, n = 8]). Normalized plasma levels relative to maximum (Cmax: diazepam 775 nM [1 h]; eszopiclone 1680 nM [0.5 h]; DORA-22 134 nM [2 h]) compare compound levels on the same y-axis scale. B. Mean time in active wake (+ SEM) determined by polysomnography in 30-min intervals after treatment (vehicle, closed symbols; compound, open symbols). Significant differences versus vehicle are indicated by gray vertical lines and tick marks (short, medium, long: P < 0.05, 0.01, 0.001, respectively). C. Mean qEEG power in gamma (35–100 Hz), theta (4–8 Hz), and delta (0.5–4 Hz) frequency bands following treatment. D. DMS measure of memory at 14 h after treatment. Data are mean proportions of completed trials during which a correct choice was made (+ SEM; n = 16, 16, and 15, respectively). Random responding, 25%. Significant differences from vehicle: * P < 0.05 (repeated measures ANOVA). E. SCRT evaluation of attention at 16 h after treatment. Data are the mean proportions of completed trials during which a correct choice was made following short duration cues (+ SEM; n = 16, 16, and 5, respectively). Random responding, 10%. Significant differences from vehicle: * P < 0.05.