A newly identified compound selectively blocks receptors for the protein that narcoleptics lack. The drug has the apparent capacity to put wakeful people to sleep.

For years, researchers interested in the regulatory mechanisms of the sleep-wake cycle have studied narcolepsy, a disorder of excessive daytime sleepiness that occurs in some mammals, including dogs, rats, and humans. Investigators led by François Jenck at Actelion Pharmaceuticals (Allschwil, Switzerland) found the drug, known as ACT-078573, after screening new compounds for the ability to block orexin receptors. Orexins are neuropeptide hormones produced by certain neurons in the brain—neurons that degenerate in human narcoleptics. One role of orexins is to regulate wakefulness, although these proteins have also been associated with modulating addictive behavior.

In separate trials, Jenck's group administered the drug orally to rats, dogs, and humans during periods of normal wakefulness (Nat. Med., February). In effect, the drug put the subjects to sleep in a dose-dependent manner. One common phenomenon associated with narcolepsy is cataplexy, a state of muscle paralysis often induced by intense emotion—mirth or fright, for instance—but no signs of cataplexy were observed in any of the study's subjects. Moreover, other side effects commonly associated with some sedatives, such as feelings of drunkenness or 'abnormal coordination', were rarely associated with the drug's use in humans.

Despite its ability to induce sleep, the drug does not appear to be a good candidate for insomnia treatment. Orexins are produced primarily during normal waking hours, and although the drug caused sleepiness when administered to dogs and rats during normal waking time, there was no such effect during normal sleep periods. Nevertheless, the drug may prove to be effective in helping shift workers, sufferers of jet lag, and others who try to sleep during daytime hours.

In addition, the drug holds promise for addicts because orexins have been implicated in addiction-associated pathways. In some studies, mice that lack orexins resist overeating and some of the behaviors typical of morphine addiction. Although this connection between orexins and addiction is still not well understood, it presents the possibility that a drug blocking the orexin receptors may be therapeutic for addicts.