Medications that improve narcolepsy target specific neurochemical systems

Narcolepsy is caused by a loss of the orexin-producing neurons in the lateral hypothalamus. Normally, the orexin neuropeptides excite neurons that promote wakefulness and suppress REM sleep including monoaminergic areas such as the locus coeruleus, raphe nuclei, ventral tegmental area, periaqueductal grey, and tuberomammillary nucleus as well as cholinergic areas such as the basal forebrain and pedunculopontine and laterodorsal tegmental nuclei (PPT/LDT). Most medications that improve sleepiness do so by enhancing dopamine signaling, and most cataplexy-suppressing medications increase norepinephrine and/or serotonin signaling.