The Molecular Basis of Insomnia: Implication for Therapeutic Approaches.
Preclinical Research Insomnia is one of the most common sleep disorders that is characterized by difficulty in sleep initiation, sleep maintenance, and/or poor sleep quality. Treatment for insomnia includes both pharmacological and non-pharmacological interventions. Recently, the development of pharmacological treatment for insomnia has been prompted by the understanding of the molecular neurobiology of sleep-wake regulation. For pharmacological treatment, benzodiazepines that target GABAergic system are the most widely used hypnotics. Besides GABA, the hypocretin/orexin system, and the hypothalamic-pituitary-adrenal (HPA) axis are involved in sleep-wake regulation and may also play important role in the pathogenesis of insomnia. Genetic studies have revealed the critical role of several important genes related to the above-mentioned systems in the regulation and function of sleep, suggesting the genetic/epigenetic factors could also contribute to the development and regulation of insomnia. Non-pharmacological interventions include cognitive behavioral therapy for insomnia (CBT-I) that is an effective insomnia treatment with less risk and side effects of drug therapy. Here the current treatments for insomnia based on the molecular mechanisms underlying sleep-wake regulation, were reviewed and some newer targets that may be beneficial in the development of new treatments for insomnia were discussed. Drug Dev Res 77 : 427-436, 2016. © 2016 Wiley Periodicals, Inc.
Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, NY.|Department of Pharmacology and Toxicology, State University of New York at Buffalo, Buffalo, NY.
Zi-Jun
ZJ
Wang
Department of Pharmacology and Toxicology, State University of New York at Buffalo, Buffalo, NY.
Jian-Feng
JF
Liu
D015928:Cognitive Behavioral Therapy; D044127:Epigenesis, Genetic; D020022:Genetic Predisposition to Disease; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D007319:Sleep Initiation and Maintenance Disorders / Q000235:genetics / Q000628:therapy*; D016896:Treatment Outcome
D006993:Hypnotics and Sedatives
HPA axis; insomnia; neurotransmitter; orexin; sleep