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Re: biomaven0 post# 130748

Thursday, 11/10/2011 4:42:27 PM

Thursday, November 10, 2011 4:42:27 PM

Post# of 257269

Aside from sleep, what other effects might this antagonist have? Any possible effect on appetite? Lipid metabolism?



The most profound data on the orexin system is in sleep/wakefulness. I did fail to mention the generic concern that orexin antagonists could have cataplexy issues, but I have not seen any such statement in any of the press releases from MRK on the program. Cataplexy showed up in some of the animal knockout work.

As to effects on lipid metabolism or on appetite, I would not expect any effect that would be commercially approvable. On appetite there is some positive data in preclinical studies, but this has been somewhat controversial and may be due to off target effects of the small molecule being studied. I am not familiar with any confirmed data in animal models on lipid control.

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