Evaluation of the abuse liability of modafinil and other drugs for excessive daytime sleepiness associated with narcolepsy.

Psychostimulants have been used routinely for the treatment of the disabling daytime sleepiness associated with narcolepsy. However, the perceived and real potential for abuse of amphetamine and amphetaminelike stimulants prompted a search for new wake-promoting compounds with lower dependency and abuse liabilities. Modafinil is a novel wake-promoting agent with a mechanism of action that differs markedly from that of amphetamine and amphetamine-like stimulants. In controlled clinical trials, modafinil has been shown to be an effective and well-tolerated treatment for excessive daytime sleepiness (EDS) in patients with narcolepsy. With a benzhydrylsulfinylacetamide structure, modafinil has a low level of solubility in water (< 1 mg/mL) and is unstable at temperatures > or = 180 degrees C, physicochemical properties that reduce the potential for its abuse via intravenous injection and smoking, respectively. Available preclinical and clinical data on the abuse liability of modafinil suggest a much lower potential for abuse and dependency than amphetaminelike stimulants commonly used for treating EDS in patients with narcolepsy. Therefore, modafinil represents a valuable therapeutic option for the treatment of EDS associated with narcolepsy.

Effects of restricted sleep with different exercise loads upon subsequent sleep.

Seven male cats were adapted to different schedules of restricted sleep. The cat was permitted to go to sleep either 2, 4 or 8 hours per day with the balance to 24-h periode spent in wakefulness enforced by means of a treadmill. Two experiments were run and the same cats served in both runs. The experiments and schedules were separated by at least two weeks during which time cats were maintained under ordinary laboratory conditions. Our experiment used treadmill speed of 2.6 m/min which was easily tolerated and effective in eliminating sleep. Another experiment used treadmill speed of 4.6 m/min which produced more physical exercise. As available sleep time become progressively shorter, REM sleep increased while SWS decreased. If restriction in sleep time was associated with more physical exercise then the composition of the subsequent sleep was different : SWS increased while REM sleep decreased. The functional significance of these opposite effects are presumably different. The immediate SWS response to the prior muscular exercise is suggestive of its recovery function.

Nonpharmacologic treatment of periodic leg movements in sleep.

The effects of a 30-minute stimulation of the dorsiflexors of the feet and toes before bedtime were investigated in eight patients with periodic leg movements in sleep (PLMS). None were taking medications at the time of the investigation. All subjects were treated with the EMS-250 Neuromuscular Stimulator, which has a maximum output per channel of 1.5mA and a frequency of 47Hz. Stimuli were delivered via a pulse train (on for 1.5sec and off for 1.8sec). A single all-night polysomnogram after this stimulation showed that all patients responded to stimulation, with reduction of leg movements from an average pretreatment PLMS index of 44.6 per hour to a posttreatment PLMS index of 14 per hour (p less than .01). Nocturnal leg movements were primarily reduced during the non-REM sleep. Multiple indices of sleep continuity did not change significantly, although there was a trend toward better sleep consolidation.