Scientists spot mechanism behind promising new sleep drug

An experimental drug called gaboxadol may soon help millions of bleary-eyed insomniacs get to sleep, and a multi-center team of U.S. scientists believes they've pinpointed just how the drug works.

Neuroscientist researchers from Weill Cornell Medical College in New York City; the University of Pittsburgh; and the University of California, Los Angeles, say gaboxadol acts in a whole different way from sleep aids such as Ambien, or older benzodiazepine drugs such as Valium.

What's more, gaboxadol's unique mechanism of action could keep it from disrupting the delicate ratio of REM to non-REM sleep - a problem plaguing many commercially available sleep aids.

Gaboxadol is currently in Phase III clinical trials as a sleep drug by Merck & Co, in partnership with the Danish company Lundbeck.

"Drugs like Ambien work on the alpha-1 subtype of receptors for the neurotransmitter GABA - that's akin to an 'on/off switch' for the central nervous system. On the other hand, gaboxadol works on another subtype, called alpha 4 - it's more of a 'dimmer switch' that might help regulate sleep in a less disruptive way," explains co-researcher Dr. Neil Harrison, Professor of Pharmacology in Anesthesiology at Weill Cornell Medical College.

He and Dr. Gregg Homanics, Associate Professor of Anesthesiology and Pharmacology at the University of Pittsburgh, are co-senior authors on the paper. Drs. Carolyn Houser, Igor Spiegelman and Richard Olsen of UCLA also contributed to this research.

The findings were published recently in the Proceedings of the National Academy of Sciences.

Each night, millions of Americans struggle with sleeplessness. According to the National Sleep Foundation (NSF), almost six of 10 Americans report having insomnia at least a few nights weekly. As many as 25 percent of people say they have used medications to help them sleep at least once in the past year.

Numerous drugs are available to help people sleep, but nearly all come with undesirable side-effects, such as lingering daytime grogginess.

The search for a drug that might faithfully mimic natural human sleep has led to gaboxadol, which was originally developed in Denmark in the 1970s as a possible anticonvulsant for use in people with epilepsy.

At the time, researchers shelved the drug, noting that it was too sedating.

It was not until the mid-1990s that Dr. Marike Lancel at the Max Planck Institute for Psychiatry in Munich, Germany, revisited gaboxadol as a possible hypnotic, or sleep aid.

"In trials, it does appear to help people get to sleep, although the exact way in which it does so has remained unclear," according to Dr. Harrison.

It appears that, like Ambien, gabodoxal works with GABA, a key central nervous system neurotransmitter that helps inhibit neuronal activity.