Research points to new, safer class of sleep aids

In tests, memory of rats, monkeys is unimpaired
2013-04-06T00:00:00Z Research points to new, safer class of sleep aidsGisela Telis Sciencenow Arizona Daily Star
April 06, 2013 12:00 am  • 

Insomniacs desperate for some zzzs may one day have a safer way to get them. Scientists have developed a new sleep medication that has induced sleep in rodents and monkeys without apparently impairing cognition, a potentially dangerous side effect of common sleep aids.

The discovery, which originated in work explaining narcolepsy, could lead to a new class of drugs that help people who don't respond to other treatments.

Between 10 percent and 15 percent of Americans chronically struggle with getting to or staying asleep. Many of them turn to sleeping pills for relief, and most are prescribed drugs, such as zolpidem (Ambien) and eszopiclone (Lunesta), that slow down the brain by binding to receptors for GABA, a neurotransmitter that's involved in mood, cognition and muscle tone.

But because the drugs target GABA indiscriminately, they can also impair cognition, causing amnesia, confusion, and other problems with learning and memory, along with a number of strange sleepwalking behaviors, including wandering, eating and driving while asleep.

Neuroscientist Jason Uslaner of Merck Research Laboratories in West Point, Pa., and colleagues decided to tap into the brain's orexin system. Orexin (also known as hypocretin) is a protein that controls wakefulness and is missing in people with narcolepsy.

Past studies successfully induced sleep by inhibiting orexin, but had not looked into its effects on cognition. The researchers developed a new orexin-inhibiting compound called DORA-22 and confirmed that it could induce sleep in rats and rhesus monkeys as effectively as the GABA-modulating drugs.

Then the researchers went about testing the drugs' effects on the animals' cognition.

They measured the rats' cognition and memory by assessing the rodents' ability to recognize objects. They presented the rats with a new object - say, a cone or a sphere. Then they took the object away. After an hour, the rats were exposed to a new object and the one they knew; if the rats remembered, they spent less time checking out the familiar object.

With the primates, researchers tested their ability to match colors and to pay attention to and identify the origin of a flashing light.

In all the cases, the researchers found the GABA-modulating sleeping pills caused both the rats and the primates to respond more slowly and less accurately.

But DORA-22 had no such effect on cognition, the team reported Wednesday in Science Translational Medicine.

"We were very excited," Uslaner says. "Folks who take sleep medications need to be able to perform cognitive tasks when they awake, and this (compound) could help them do so without impairment."

Although DORA-22 has not yet been tested in humans, it holds tremendous promise, says Emmanuel Mignot, a sleep researcher with the Stanford University School of Medicine in Palo Alto, California.

"This study is encouraging and exciting, because there's good reason to believe it would work differently from what we've used in the past," says Mignot, who helped discover the link between orexin (or its absence) and narcolepsy. "Not every drug works for everyone, so it's really, really good news to have a potential new drug on the horizon."

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