Dual orexin receptor (OXR) antagonists (DORAs) such as almorexant, SB-649868 or suvorexant, have shown promise for the treatment of insomnias and sleep disorders in several recent clinical trials in volunteers and primary insomnia patients. The relative contribution of antagonism of both OX1R and OX2R for sleep induction is still a matter of debate. We therefore initiated a drug discovery project with the aim of creating both OX2R selective and DORAs. Here we report that the OX2R selective antagonist 26 induced sleep in mice primarily by increasing NREM sleep, whereas the DORA suvorexant induced sleep largely by increasing REM sleep. Thus, OX2R selective antagonists may also be beneficial for the treatment of insomnia