Narcolepsy: Neuropharmacological Aspects

AbstractNarcolepsy (affects 1/2000 of the general population) is characterized by excessive daytime sleepiness, cataplexy, and other dissociated manifestations of rapid eye movement sleep (hypnagogic hallucinations and sleep paralysis). The disease is currently treated with amphetamine‐like compounds and modafinil for EDS and anticataplectics (antidepressants) for cataplexy. The major pathophysiology of human narcolepsy has recently been revealed by the extension of discoveries of narcolepsy genes in animal models: about 90% of human narcolepsy‐cataplexy has been found to be hypocretin/orexin ligand deficient. This directly led to the development of new diagnostic tests (i.e., CSF hypocretin measures). Hypocretin replacement is also likely to be a new therapeutic option for hypocretin deficient narcolepsy, but this is still not available in humans. Clinical and pharmacological aspects of narcolepsy as well as future directions are discussed.