title: Cerebral blood flow changes in man by wake-promoting drug, modafinil: a randomized double blind study.
abstract: To investigate the effects of a wake-promoting drug, modafinil on regional cerebral blood flow (rCBF) in healthy volunteers, we performed (99m)Tc-ethylcysteinate dimer single photon emission computed tomography (SPECT) before and after modafinil or placebo administration. Twenty-one healthy subjects received single doses of 400 mg modafinil or placebo in a double blind randomized crossover study design. Administrations of modafinil or placebo in a subject were separated by a 2-week washout. Brain SPECT was performed twice before and 3 h after modafinil or placebo administration. For statistical parametric mapping analysis, all SPECT images were spatially normalized to the standard SPECT template and then smoothed using a 12-mm full width at half-maximum Gaussian kernel. The paired t-test was used to compare pre- versus post-modafinil and pre- versus post-placebo SPECT images. Differences in rCBF between post-modafinil and post-placebo conditions were also tested. Modafinil decreased Epworth and Stanford sleepiness scales whereas placebo did not. The post-modafinil condition was associated with increased rCBF in bilateral thalami and dorsal pons, whereas the post-placebo condition showed increased rCBF in a smaller area of the dorsal pons when compared with the drug naïve baseline condition. Compared with the post-placebo condition, the post-modafinil condition showed higher rCBF in bilateral frontopolar, orbitofrontal, superior frontal, middle frontal gyri, short insular gyri, left cingulate gyrus, left middle/inferior temporal gyri, left parahippocampal gyrus, and left pons. In healthy volunteers, modafinil increased wakefulness and rCBF in the arousal-related systems and in brain areas related to emotion and executive function.
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Eun Yeon
authors.initials: EY
authors.lastname: Joo
authors.forename: Woo Suk
authors.initials: WS
authors.lastname: Tae
authors.forename: Ki-Young
authors.initials: KY
authors.lastname: Jung
authors.forename: Seung Bong
authors.initials: SB
authors.lastname: Hong
mesh_terms: D000161:Acoustic Stimulation; D000328:Adult; D001559:Benzhydryl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology / Q000627:therapeutic use*; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D006970:Disorders of Excessive Somnolence / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology; D004311:Double-Blind Method; D004833:Epilepsy, Temporal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008032:Limbic System / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D000077408:Modafinil; D009290:Narcolepsy / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism; D010775:Photic Stimulation; D011930:Reaction Time / Q000187:drug effects; D015899:Tomography, Emission-Computed, Single-Photon; D014851:Wakefulness / Q000187:drug effects*
chemical_list: D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D005947:Glucose; D000077408:Modafinil