Electroencephalographic effects of modafinil, an alpha-1-adrenergic psychostimulant, on the sleep of rhesus monkeys.
An electroencephalographic (EEG) study on the rhesus monkey, primate model of human sleep, showed the significant wakening effect of a new psychostimulant, Modafinil. The first experiment, with single administration of three increasing doses of Modafinil (3, 6, and 12 mg/kg), was to determine the efficient threshold dose; the second experiment, with repeated administration of 22.5 mg/kg during 4 days, was to determine whether continuous wakefulness could be obtained without apparent behavioral disorders. Results of the first experiment showed a wakening effect above 6 mg/kg, but 12 mg/kg induced a sharp wakening effect with a significant decrease in all sleep stages. The second experiment induced important insomnia in all subjects for 4 days and 4 nights. No behavioral disorder was observed. Modafinil has a wakening effect at the dose of 6 mg/kg in rhesus monkeys and induces quasicontinuous wakefulness for 4 total days and nights with daily administration of 22.5 mg/kg, with no behavioral disorders. Modafinil should therefore find interesting applications in sleep disorder treatments.
Lagarde
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D
Division de Neurophysiologie Appliquée, Centre d'Essais en Vol, Bretigny Sur Orge, France.
Milhaud
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C
D000818:Animals; D001143:Arousal / Q000187:drug effects; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D000697:Central Nervous System Stimulants; D002540:Cerebral Cortex / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects*; D005071:Evoked Potentials / Q000187:drug effects; D008253:Macaca mulatta; D008297:Male; D008838:Microcomputers; D000077408:Modafinil; D012815:Signal Processing, Computer-Assisted / Q000295:instrumentation; D012894:Sleep Stages / Q000187:drug effects*; D014851:Wakefulness / Q000187:drug effects
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D000077408:Modafinil