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Sleep tight: New class of sleeping pills could reduce morning "hangovers."     

New sleep aid could tackle insomnia without the morning hangover

by Matthew Ross Gelfand
May 14, 2013

A new class of sleep aids could result from the discovery of a culprit linked to insomnia – the protein orexin.

Scientists at Merck Research Laboratories in West Point, Pa., report that blocking the protein in rats leads to sleep and Merck is researching drugs that can cause drowsiness and sleep without a hangover, based on this finding.

Researchers at Merck  are developing the new compound that reduces the negative after-effects associated with current sleep aids, such as drowsiness and amnesia, by tapping into the protein in the brain that controls wakefulness.

While the results represent a potential step forward in the realm of sleep aids, the compound DORA-22 is still in the early stages of research and has not yet been tested in humans

Merck’s findings, published in Science Translational Medicine this spring, discovered that inhibiting orexin in the brain induced sleep in rats without affecting their cognition upon waking as much as current sleep aids on the market, such as Ambien and Lunesta.

Orexin receptors are missing in the brains of people with narcolepsy, an illness that causes people to dose off. The trick is to beat wakefulness but make sure people feel wide awake in the morning.

Researchers exposed rats to the orexin-inhibiting DORA-22, and then presented them with a certain object, which they were allowed to sniff. They then removed the object and, an hour later, returned with the same object, as well as a new one. If the rat spent less time sniffing the original object, scientists could infer that it was recalled it from the prior event.

The problem with current sleep aids is that they target GABA receptors, a neurotransmitter involved in mood and cognition, which can lead to a number of side effects. Rats exposed to compounds that target GABA receptors responded less accurately and more slowly in differentiating objects. 

The U.S. Food and Drug Administration recently reported this in a safety announcement that instructed users of Zolpidem, (the generic form of Ambien) to reduce bedtime doses. The announcement related to data that found the drug can impair alertness needed by the morning for activities such as driving.

Specifically, the FDA required Ambien manufacturer Sanofi Aventis U.S. to lower the recommended dose in women from 10 milligrams per day to 5 milligrams for its immediate-release products, and 12.5 milligrams to 6.25 milligrams for extended release medication. Lower dosage was recommended but not required for males.

“The three main issues with current sleeping pills involve tolerance, abuse and hangover effects, said Dr. W. Vaughn McCall, chair of the Medical College of Georgia Department of Psychiatry and Health Behavior and Georgia Regents University. “The DORA-22 pills don’t carry the same addiction potential and are more clean, with less of that ‘hangover’ feeling,” said McCall, who is not associated with the Merck research.

McCall was one of the lead researchers in another study published in the Journal of Clinical Sleep Medicine that linked insomnia to suicidal ideations. He measured symptoms of depression, hopelessness and insomnia in 50 patients who had all previously been treated for a depressive disorder, and found a positive association between dysfunctional beliefs about sleep and thoughts of suicide.

“Sleep is very symptomatic of other illnesses,” said Alexa James, Associate Director at NAMI Greater Chicago. James suggested that the correlation between sleep problems and depression is reciprocal, in that a lack of sleep could lead to depression, and vice versa.

McCall also noted that not many doctors are trained specifically in counseling insomnia, leading to sometimes haphazard prescriptions for sleep aids like Ambien.

However, Dr. Puneet Opal, associate professor of Neurology and Physiology at Northwestern University’s Feinberg School of Medicine, said he would consider prescribing this new class of drugs.

“These findings represent a totally different way of looking at sleep issues and is definitely worth trying if approved,” he said.

The Stanford University School of Medicine Center for Narcolepsy is researching the effects orexin has on narcolepsy.