Neuropeptides as Possible Targets in Sleep Disorders: Special Emphasis on Hypocretin-Deficient Narcolepsy

Author(s): Nobuhiro Fujiki, Seiji Nishino

Journal Name: CNS & Neurological Disorders - Drug Targets
Formerly Current Drug Targets - CNS & Neurological Disorders

Volume 6 , Issue 1 , 2007

Become EABM
Become Reviewer
Call for Editor


Sleep disorders are disturbances of usual sleep patterns or behaviors caused by deregulation of neuronal synchronicity and of the balance of the neurotransmitter system involved in sleep regulation. Insomnia and hypersomnia are frequent sleep disorders, and these are most often treated pharmacologically with hypnotics and wake-promoting compounds. These compounds act on classical neurotransmitter systems, such as benzodiazepines on gamma amino butyric acid (GABA)A receptors, and amphetamine-like stimulants on monoaminergic terminals to modulate neurotransmission. In addition, acetylcholine, amino acids, lipids and proteins (cytokines) and peptides, are known to significantly modulate sleep, and thus, are possibly involved in the pathophysiology of some sleep disorders. Due to recent developments in molecular biological techniques, many neuropeptides have been newly identified, and some are found to significantly modulate sleep. Recent discoveries also include the finding that the impairment of hypocretin/orexin neurotransmission (a recently isolated hypothalamic neuropeptide and receptor system), is the major pathophysiology of narcolepsy with cataplexy. A hypocretin replacement therapy is anticipated to reverse the disease symptoms in humans. In this article, we will review the history of neuropeptide research, sleep modulatory effects of various neuropeptides, and the general strategies for the pharmacological therapeutics targeting the peptidergic systems by referring to hypocretin-deficient narcolepsy as an immediate example.

Keywords: Sleep disorders, neuropeptide, GPRC, hypocretin, orexin, narcolepsy

promotion: free to download

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2007
Page: [45 - 62]
Pages: 18
DOI: 10.2174/187152707779940781

Article Metrics

PDF: 16