The sleep promoting effect of DORAs is the result of the inhibition of orexin-induced arousal primarily mediated through OX2R. Genetically, loss of this receptor is associated with narcolepsy in dogs [36] and the hypersomnolent phenotype of mice lacking OX2R is similar to that of those lacking both receptors or Hcrt gene encoding orexin ligands [37,38], while OX1R KOs reportedly display only a minor, sleep fragmentation phenotype [39]. This evidence concerns the gene HCRTR2 and narcolepsy.