Effect of a novel histamine subtype-3 receptor inverse agonist and modafinil on EEG power spectra during sleep deprivation and recovery sleep in male volunteers.
Author(s): James LM, Iannone R, Palcza J, Renger JJ, Calder N, Cerchio K, Gottesdiener K, Hargreaves R, Murphy MG, Boyle J, Dijk DJ
Affiliation(s): Surrey Sleep Research Centre, Faculty of Health and Medical Sciences, University of Surrey, Egerton Road, Guildford, GU2 7XP, UK.
Publication date & source: 2011-06, Psychopharmacology (Berl)., 215(4):643-53. Epub 2011 Feb 8.
Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't
RATIONALE: Histamine and dopamine contribute to the maintenance of wakefulness. OBJECTIVE: This 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. METHODS: A 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. RESULTS: After 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. CONCLUSION: Both MK-0249 and modafinil exert effects on the EEG which are consistent with wake promotion.