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.