Armodafinil, the R-enantiomer of modafinil: Wake-promoting effects and pharmacokinetic profile in the rat
Wisor JP, Dement WC, Aimone L, Williams M, Bozyczko-Coyne D.
Stanford Sleep Disorders Clinic and Research Laboratory,
701 Welch Rd., Suite 2226, Stanford,
CA 94304, United States.
Pharmacol Biochem Behav. 2006 Nov 27;
ABSTRACTModafinil reduces the excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome, and shift work sleep disorder. In rats, modafinil promotes dose-dependent increases in wake duration. The wake-promoting activity of the R-enantiomer of modafinil (armodafinil) was evaluated in WKY rats and compared to the classical stimulant, d-methamphetamine. Electroencephalographic and electromyographic signals were assessed via a tethered cranial implant. Body temperature and locomotor activity were assessed by telemetry via intraperitoneal implant. Rats (n=60, 12 per group) were subjected to one of five parallel treatments: armodafinil at 30, 100 and 300 mg/kg i.p.; d-methamphetamine, 1 mg/kg i.p. and vehicle. Armodafinil and d-methamphetamine increased time spent awake relative to vehicle. Armodafinil-evoked increases in wake duration were dose-dependent and proportional to plasma compound exposure. Induction of wakefulness by d-methamphetamine was associated with an approximately two-fold increase in locomotor activity during the 2-h period immediately following administration relative to vehicle. d-methamphetamine also increased body temperature over the same time interval. The dose of armodafinil (100 mg/kg, i.p.) that was closest to d-methamphetamine in its wake-promoting efficacy did not produce changes in either body temperature or the intensity of locomotor activity relative to vehicle. Acute rebound hypersomnolence, characterized by increases in non-rapid eye movement sleep (NREMS) as a percentage of time and NREMS bout duration and by a decreased frequency of brief awakenings following sleep deprivation, occurred following d-methamphetamine-but not armodafinil-induced wake in this rat model which has been shown to be predictive of human drug responses.Narcolepsy
Modafinil and serotonin
Modafinil and the marmoset
Excessive daytime sleepiness
Modafinil as an antidepressant
Modafinil versus amphetamine
Modafinil versus methylphenidate
Modafinil, amphetamine and sleep