title: 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.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  Both MK-0249 and modafinil exert effects on the EEG which are consistent with wake promotion.
authors.affiliation: Surrey Sleep Research Centre, Faculty of Health and Medical Sciences, University of Surrey, Egerton Road, Guildford, GU2 7XP, UK.
authors.forename: Lynette M
authors.initials: LM
authors.lastname: James
authors.forename: Robert
authors.initials: R
authors.lastname: Iannone
authors.forename: John
authors.initials: J
authors.lastname: Palcza
authors.forename: John J
authors.initials: JJ
authors.lastname: Renger
authors.forename: Nicole
authors.initials: N
authors.lastname: Calder
authors.forename: Kristine
authors.initials: K
authors.lastname: Cerchio
authors.forename: Keith
authors.initials: K
authors.lastname: Gottesdiener
authors.forename: Richard
authors.initials: R
authors.lastname: Hargreaves
authors.forename: M Gail
authors.initials: MG
authors.lastname: Murphy
authors.forename: Julia
authors.initials: J
authors.lastname: Boyle
authors.forename: Derk-Jan
authors.initials: DJ
authors.lastname: Dijk
mesh_terms: D000293:Adolescent; D000328:Adult; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D018592:Cross-Over Studies; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D054314:Drug Inverse Agonism; D004569:Electroencephalography; D017442:Histamine Agonists / Q000494:pharmacology*; D054828:Histamine H3 Antagonists / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D012892:Sleep Deprivation / Q000378:metabolism / Q000503:physiopathology*; D012894:Sleep Stages / Q000187:drug effects*; D014851:Wakefulness / Q000187:drug effects; D055815:Young Adult
chemical_list: D001559:Benzhydryl Compounds; D015259:Dopamine Agents; D017442:Histamine Agonists; D054828:Histamine H3 Antagonists; D018100:Receptors, Histamine H3; D000077408:Modafinil