In a study published in Science Translational Medicine, researchers from Merck have found that an experimental agent called DORA-22 can promote sleep in both rhesus monkeys and rats, without affecting memory or reaction time. DORA-22 is part of a new class of drugs the FDA is considering approval for called orexin antagonists. The authors compared the sleep-inducing effects of DORA-22 to those of well-known sleeping pills including zolpidem (Ambien), diazepam (Valium) and eszopiclone (Lunesta). These current drugs work by slowing down brain activity. What makes this new class of drugs different? “DORA binds to orexin receptors in the brain, which are located in areas that control sleep and wakefulness,” says John Renger, a co-author of the study and executive director of science at Merck. “At night orexin levels (normally) go down. DORA works by mimicking what happens in the normal system where signaling in this system goes away at night.” In contrast, most current sleep drugs affect GABA, which is one of the most prevalent brain chemicals in the brain, and associated with calming the brain. Activating GABA can induce sleep, but it can also cloud thinking and memory.

Merck is also studying other agents that work on the orexin system, that are farther along in human testing than DORA-22. Three successful clinical trials have been conducted with a compound called suvorexant, and the FDA will consider these results as well. Renger says that currently the late stage findings show that suvorexant helps people get to sleep faster and has increased the time the patients stay asleep, compared to placebo. While there is no target date for these drugs to go on the market, there is anticipation it will happen. “It’s very enticing because there are some clear results that show that these drugs differ from old hypnotic drugs in terms of affecting cognition and memory in two animal species,” says Dr. Emmanuel Mignot, director of the Stanford Center for Sleep Sciences, who wrote a commentary on the research, which was published in Science…….  healthland.time.com    4/5/13

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