(A) A schematic drawing showing the location of the orexin neurons in the lateral hypothalamus and the loss of orexin neurons in a patient with type 1 narcolepsy. (B) Shows a schematic view of the orexin gene, which contains the sequences for both the orexin A and orexin B peptides. Orexin A acts on both receptors, OX1R and OX2R, but orexin B acts mainly on OX2R. OX2R has been associated mainly with wake-sleep regulation and OX1R with reward seeking and addiction behavior. Dual orexin receptor antagonists are being used clinically to treat insomnia, but specific OX1R antagonists are under development to treat addiction and OX2R agonists are being tested for treating type 1 narcolepsy and may be useful in other disorders of increased daytime sleepiness. Adapted with permission from the New England Journal of Medicine (12).