• Lynette M James, Robert Iannone, John Palcza, John J Renger, Nicole Calder, Kristine Cerchio, Keith Gottesdiener, Richard Hargreaves, M Gail Murphy, Julia Boyle, and Derk-Jan Dijk.
• Surrey Sleep Research Centre, Faculty of Health and Medical Sciences, University of Surrey, Egerton Road, Guildford, GU2 7XP, UK.
• Psychopharmacology (Berl.). 2011 Jun 1;215(4):643-53.

RationaleHistamine and dopamine contribute to the maintenance of wakefulness.ObjectiveThis study aims to conduct an exploratory analysis of the effects of 10 and 50 mg of MK-0249, a novel histamine subtype-3 receptor inverse agonist, and 200 mg of modafinil, a presumed dopaminergic compound, on EEG power spectra during sleep deprivation and subsequent recovery sleep.MethodsA total of 25 healthy men were recruited to a double-blind, placebo-controlled cross-over design. EEG power spectra, an electrophysiological marker of changes in sleepiness and vigilance, were obtained at the beginning of wake maintenance tests at two-hourly intervals throughout a night and day of sleep deprivation, which is an established model of excessive sleepiness.ResultsAfter placebo, sleep deprivation was associated with enhancements in delta and theta and reductions in alpha and beta activity. Following dosing at 02:00 h, MK-0249 and modafinil reduced delta and theta activity and enhanced alpha and beta activity, compared to placebo. During recovery sleep initiated at 21:00 h, latency to sleep onset and number of awakenings were not different from placebo for any of the active treatments. Wake after sleep onset and stage 1% was increased and total sleep time, SWS% and REM% were reduced after both doses of MK-0249. Compared to placebo, MK-0249, the 50-mg dose in particular, reduced activity in some delta and theta/alpha frequencies and enhanced beta activity during NREM sleep and REM sleep. After modafinil, no changes were observed for power spectra during sleep.ConclusionBoth MK-0249 and modafinil exert effects on the EEG which are consistent with wake promotion.

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