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

Psychopharmacology (Berl). 2011 Jun;215(4):643-53. doi: 10.1007/s00213-010-2158-3. Epub 2011 Feb 8.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Benzhydryl Compounds / pharmacology*
  • Cross-Over Studies
  • Dopamine Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Inverse Agonism
  • Electroencephalography
  • Histamine Agonists / pharmacology*
  • Histamine H3 Antagonists / pharmacology*
  • Humans
  • Male
  • Middle Aged
  • Modafinil
  • Receptors, Histamine H3 / metabolism*
  • Sleep Deprivation / metabolism
  • Sleep Deprivation / physiopathology*
  • Sleep Stages / drug effects*
  • Wakefulness / drug effects
  • Young Adult


  • Benzhydryl Compounds
  • Dopamine Agents
  • Histamine Agonists
  • Histamine H3 Antagonists
  • Receptors, Histamine H3
  • Modafinil