Journal
SLEEP MEDICINE
Volume 8, Issue 4, Pages 373-399Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.sleep.2007.03.008
Keywords
narcolepsy
Categories
Funding
- NIMH NIH HHS [R01 MH072525, R01 MH072525-01A2, 1R01MH72525] Funding Source: Medline
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Narcolepsy is characterized by excessive daytime sleepiness (EDS), cataplexy and/or other dissociated manifestations of rapid eye movement (REM) sleep (hypnagogic hallucinations and sleep paralysis). Narcolepsy is currently treated with amphetamine-like central nervous system (CNS) stimulants (for EDS) and antidepressants (for cataplexy). Some other classes of compounds such as modafinil (a non-amplietamine wake-promoting compound for EDS) and gamma-hydroxybutyrate (GHB, a short-acting sedative for EDS/fragmented nighttime sleep and cataplexy) given at night are also employed. The major pathophysiology of human narcolepsy has been recently elucidated based on the discovery of narcolepsy genes in animals. Using forward (i.e., positional cloning in canine narcolepsy) and reverse (i.e., mouse gene knockout) genetics, the genes involved in the pathogenesis of narcolepsy (hypocretin/orexin ligand and its receptor) in animals have been identified. Hypocretins/orexins are novel hypothalamic neuropeptides also involved in various hypothalamic functions such as energy homeostasis and neuroendocrine functions. Mutations in hypocretin-related genes are rare in humans, but hypocretin-ligand deficiency is found in many narcolepsy-cataplexy cases. In this review, the clinical, pathophysiological and pharmacological aspects of narcolepsy are discussed. (c) 2007 Elsevier B.V. All rights reserved.
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