title: Acute alertness-promoting effects of a novel histamine subtype-3 receptor inverse agonist in healthy sleep-deprived male volunteers.
abstract: The alertness-promoting effect of MK-0249 (10 or 50 mg), a histamine subtype-3 receptor (HRH3) inverse agonist (IA), was evaluated in the stimulant reference sleep deprivation model (SRSDM) using a double-blind, double-dummy, placebo- and modafinil- (200 mg) controlled, four-period crossover design in 24 healthy young men. The two primary hypotheses were related to sleep latency (first appearance of one epoch of stage 2, 3, or 4 or REM sleep, as detected using polysomnography (PSG)) at 8:00 AM on day 2. Statistically significant increases in sleep latency were observed in association with the use of modafinil 200 mg (9.07 min; P < 0.0001), MK-0249 50 mg (5.17 min; P = 0.008), and MK-0249 10 mg (5.45 min; P = 0.005) at the maintenance of wakefulness test (MWT) at 8:00 AM. Sleep latency was higher when averaged over all MWT time points (P < 0.0001 for modafinil and for both doses of MK-0249). The alertness-promoting effect with the use of MK-0249 in the SRSDM suggests that HRH3 IAs may be effective in disorders involving excessive somnolence.
authors.affiliation: Merck Research Laboratories, West Point, Pennsylvania, USA. robert_iannone@merck.com
authors.forename: R
authors.initials: R
authors.lastname: Iannone
authors.forename: J
authors.initials: J
authors.lastname: Palcza
authors.forename: J J
authors.initials: JJ
authors.lastname: Renger
authors.forename: N
authors.initials: N
authors.lastname: Calder
authors.forename: K
authors.initials: K
authors.lastname: Cerchio
authors.forename: K
authors.initials: K
authors.lastname: Gottesdiener
authors.forename: R
authors.initials: R
authors.lastname: Hargreaves
authors.forename: D J
authors.initials: DJ
authors.lastname: Dijk
authors.forename: J
authors.initials: J
authors.lastname: Boyle
authors.forename: M G
authors.initials: MG
authors.lastname: Murphy
mesh_terms: D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D054314:Drug Inverse Agonism; D017442:Histamine Agonists / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018100:Receptors, Histamine H3 / Q000502:physiology*; D012892:Sleep Deprivation / Q000188:drug therapy* / Q000503:physiopathology; D012894:Sleep Stages / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
chemical_list: D017442:Histamine Agonists; D018100:Receptors, Histamine H3