MONDAY, Jan. 29 (HealthDay News) -- The first orally active, brain-penetrating antagonist of the hypothalamic orexin pathway triggers electrophysiological signs of sleep in rats, dogs and humans, according to an advance online study published Jan. 28 in Nature Medicine.
Since low brain levels of orexins have been observed in patients with narcolepsy, Francois Jenck, Ph.D., of Actelion Pharmaceuticals Ltd. in Allschwil, Switzerland, and colleagues tested whether a dual antagonist of both orexin 1 and orexin 2 receptors had an effect on alertness in Wistar rats, beagle dogs, and in a group of 42 male humans.
The investigators found that inhibitors triggered a decrease in alertness in all three species, indicated by clinical signs of somnolence, and caused electrophysiological markers of non-REM and REM sleep in rats. The blocker was more efficient and had fewer secondary effects than other sleep-promoting agents like zolpidem. In contrast to narcolepsy, no signs of cataplexy were observed.
"It is proposed that this small molecule will serve as a useful agent in delineating further physiological and pathophysiological roles of endogenous orexins in the mammalian brain," the authors write.
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