title: Acute sleep deprivation: the effects of the AMPAKINE compound CX717 on human cognitive performance, alertness and recovery sleep.
abstract: AMPA receptor modulation is a potential novel approach to enhance cognitive performance. CX717 is a positive allosteric modulator of the AMPA receptor that has shown efficacy in rodent and primate cognition models. CX717 (100 mg, 300 mg and 1000 mg) and placebo were studied in 16 healthy male volunteers (18-45 years) in a randomized, crossover study. Cognitive function, arousal and recovery sleep (by polysomnography) were assessed during the extended wakefulness protocol. Placebo condition was associated with significant decrements in cognition, particularly at the circadian nadir (between 03:00 and 05:00). Pre-specified primary and secondary analyses (general linear mixed modelling, GLMM) at each separate time point did not reveal consistent improvements in performance or objective alertness with any dose of CX717. Exploratory repeated measures analysis, a method used to take into account the influence of individual differences, demonstrated an improvement in attention-based task performance following the 1000 mg dose. Analysis of the recovery sleep showed that CX717 1000 mg significantly reduced stage 4 and slow-wave sleep (p ≤ 0.05) with evidence of reduced electroencephalogram (EEG) slow-wave and spindle activity. The study suggests that CX717 only at the 1000 mg dose may counteract effects of sleep deprivation on attention-based tasks and that it may interfere with subsequent recovery sleep.
authors.affiliation: Surrey Clinical Research Centre, Division of Clinical Medicine, Faculty of Health and Medical Sciences University of Surrey, Guildford, Surrey, UK. j.boyle@surrey.ac.uk
authors.forename: Julia
authors.initials: J
authors.lastname: Boyle
authors.forename: Neil
authors.initials: N
authors.lastname: Stanley
authors.forename: Lynette M
authors.initials: LM
authors.lastname: James
authors.forename: Nicola
authors.initials: N
authors.lastname: Wright
authors.forename: Sigurd
authors.initials: S
authors.lastname: Johnsen
authors.forename: Emma L
authors.initials: EL
authors.lastname: Arbon
authors.forename: Derk-Jan
authors.initials: DJ
authors.lastname: Dijk
mesh_terms: D000293:Adolescent; D000328:Adult; D000494:Allosteric Regulation / Q000187:drug effects; D001143:Arousal / Q000187:drug effects*; D058256:Brain Waves / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects / Q000379:methods / Q000523:psychology; D006801:Humans; D007555:Isoxazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use; D017286:Polysomnography / Q000187:drug effects / Q000379:methods; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology; D018091:Receptors, AMPA / Q000819:agonists; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D012892:Sleep Deprivation / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D014851:Wakefulness / Q000187:drug effects* / Q000502:physiology
chemical_list: C542518:CX717; D007555:Isoxazoles; D018697:Nootropic Agents; D018091:Receptors, AMPA