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Jan 28, 2010
 |  BC Innovations  |  Targets & Mechanisms

Putting anxiety to rest

Orexin's role in narcolepsy and appetite has made receptors for the neuropeptide attractive targets for sleep and diet disorders. Now, a report from Indiana University researchers has shown that one of the brain hormone's two receptors-orexin 1 receptor-is a key player in panic and anxiety.1 Companies with orexin receptor antagonists in the clinic for sleep disorders thus have an opportunity to test their compounds for anxiolytic effects.

Orexin, also known as hypocretin, is produced in the lateral hypothalamus in response to a variety of hormonal cues about energy balance. Orexin raises alertness and appetite by activating two closely related receptors: orexin 1 receptor (OX1R) and OX2R.

Researchers have known since the 1990s that orexin receptor knockout mice, as well as Doberman pinschers with loss-of-function mutations in the orexin receptor genes, were prone to narcolepsy. In 1998, researchers at The University of Texas Southwestern Medical Center at Dallas showed that excessive orexin activity made rats hyperactive and prone to overeating.

Anantha Shekhar, professor and associate dean of translational research at the Indiana University School of Medicine, made a subtle observation from the previous rodent studies of orexin knockouts.

"It...

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