Jason M Uslaner, Spencer J Tye, Donnie M Eddins, Xiaohai Wang, Steven V Fox, Alan T Savitz, Jacquelyn Binns, Christopher E Cannon, Susan L Garson, Lihang Yao, Robert Hodgson, Joanne Stevens, Mark R Bowlby, Pamela L Tannenbaum, Joseph Brunner, Terrence P Mcdonald, Anthony L Gotter, Scott D Kuduk, Paul J Coleman, Christopher J Winrow, John J Renger
Current treatments for insomnia, such as zolpidem (Ambien) and eszopiclone (Lunesta), are γ-aminobutyric acid type A (GABAA)-positive allosteric modulators that carry a number of side effects including the potential to disrupt cognition. In an effort to develop better tolerated medicines, we have identified dual orexin 1 and 2 receptor antagonists (DORAs), which promote sleep in preclinical animal models and humans. We compare the effects of orally administered eszopiclone, zolpidem, and diazepam to the dual orexin receptor antagonist DORA-22 on sleep and the novel object recognition test in rat, and on sleep and two cognition tests (delayed match to sample and serial choice reaction time) in the rhesus monkey...
April 3, 2013: Science Translational Medicine