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A sleep drug that doesn't fog the brain?

April 04, 2013|By Melissa Healy

Prescription sleep medications can be balm for the insomniac, but for many who take medications marketed as Ambien, Restoril and Lunesta, they can come with a cost: fogginess that can last into the next day. An experimental medication may help induce sleep without the hangover of impaired attention, memory and learning that is common with so-called hypnotic sedatives now available to consumers.

The investigational drug works on receptors in a region of the brain that's key for allowing us to fall into slumber: the lateral hypothalamus, where molecules called orexins are released throughout the day to keep us alert and awake. The medication, dubbed DORA-22, suppresses the activity of orexins in the lateral hypothalamus, allowing the consumer to drop off to sleep. Existing hypnotic sedatives work on so-called GABA receptors, which are found throughout the brain. That makes them a relative blunderbuss in inducing sleep and often results in residual effects.

Those effects prompted the FDA recently to order changes to the recommended dosing of Ambien, particularly for women and the elderly, among whom lingering cognitive effects have proved to be common.

In a study released Wednesday in the journal Science Translational Medicine, a team from Merck, the pharmaceutical company developing the new medication, demonstrated its effectiveness in inducing sleep in rats and rhesus monkeys. They found that, compared with rats and rhesus monkeys administered the sleep medications zolpidem (the generic name for Ambien), eszopiclone (Lunesta), or the sleep-inducing anti-anxiety drug diazepam (better known by its commercial name, Valium), those taking the experimental sleep drug had improved sleep without impairment of their cognitive performance.

The researchers showed that the minimum effective dose of DORA-22 to induce sleep had no effect on the animals' attention and memory performance after it was administered. In the case of the widely marketed hypnotics, the minimal dose to induce sleep also resulted in cognitive deficits.

Merck is asking the Food and Drug Administration to consider approval of a proposed sleep medication, called suvorexant, with a similar mechanism of action to that of the DORA-22 medication.

While the habit-forming properties of the medication, as well as its safety and effectiveness in humans, is far from demonstrated, the prospect of a sleep aid that does not cause residual brain fog prompted Dr. Emmanuel Mignot, director of Stanford University's Center for Sleep Sciences and Medicine, to ask in an accompanying editorial if orexin-targeting sleep aids might be "the perfect hynotic."

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