Several pharmaceutical companies are working on new approaches to treat insomnia in the U.S., The Wall Street Journal reported.

The compounds are meant to work differently than current leading sleep aids such as Ambien and Lunesta, which, while generally safe, can have troubling side effects because they act on many areas of the brain.

By contrast, many of the drugs being developed target particular systems responsible for sleep and wakefulness. The hope is that they will have fewer side effects and less potential for addiction and cognition problems the next day.

Merck & Co. is investigating a compound that interferes with the activity of orexin, a chemical in the brain that produces alertness. The company hopes to file for Food and Drug Administration (FDA) approval by next year. Last fall, Somaxon Pharmaceuticals Inc. launched Silenor, a drug that blocks histamine receptors, which are important in regulating wakefulness. Neurim Pharmaceuticals Ltd. is seeking FDA approval of Circadin, a prescription form of the sleep-promoting hormone melatonin.

Other research efforts are targeting specific serotonin receptors, a move that could promote deeper stages of sleep. There is also growing interest in a form of cognitive behavioral therapy that treats insomnia.

The most common sleep-aid drugs alter the activity of a neurotransmitter that is thought to facilitate sleep. These are sedatives that "slow the brain down and put it to sleep," says James K. Walsh, executive director and senior scientist of sleep medicine at St. Luke's Hospital in St. Louis, who has done consulting work with various drug companies.

Those drugs are effective, doctors have said, but can come with significant side effects including daytime drowsiness, sometimes called the hangover effect, and memory and balance problems.

They can be dangerous when combined with other sedatives, notably alcohol, and there are some concerns that the medications can be addictive and abused.

"Often you get the story that it worked for a few weeks, then it stopped working and [the patient has] to take more," says Michael J. Sateia, professor of psychiatry, sleep medicine at Dartmouth Medical School, who has done work for some drug companies.

Drug companies say they expect the compounds being developed will have fewer side effects, be less addictive and interact less with alcohol. They say early clinical trials have so far supported those hypotheses, although evidence is preliminary.

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