Orexin (Hypocretin) Receptor Agonists and Antagonists for Treatment of Sleep Disorders : Rationale for Development and Current Status.

06:00 EST 30th January 2013 | BioPortfolio

Summary of "Orexin (Hypocretin) Receptor Agonists and Antagonists for Treatment of Sleep Disorders : Rationale for Development and Current Status."

Orexin A and orexin B are hypothalamic neuropeptides initially identified as endogenous ligands for two orphan G-protein coupled receptors (GPCRs). They play critical roles in the maintenance of wakefulness by regulating function of monoaminergic and cholinergic neurons that are implicated in the regulation of wakefulness. Loss of orexin neurons in humans is associated with narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and cataplexy, further suggesting the particular importance of orexin in the maintenance of the wakefulness state. These findings have encouraged pharmaceutical companies to develop drugs targeting orexin receptors as novel medications of sleep disorders, such as narcolepsy and insomnia. Indeed, phase III clinical trials were completed last year of suvorexant, a non-selective (dual) antagonist for orexin receptors, for the treatment of primary insomnia, and demonstrate promising results. The New Drug Application (NDA) for suvorexant has been submitted to the US FDA. Thus, the discovery of a critical role played by the orexin system in the regulation of sleep/wakefulness has opened the door of a new era for sleep medicine.


Department of Molecular Neuroscience and Integrative Physiology, Faculty of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8640, Japan, mieda@med.kanazawa-u.ac.jp.

Journal Details

This article was published in the following journal.

Name: CNS drugs
ISSN: 1172-7047


PubMed Articles [27939 Associated PubMed Articles listed on BioPortfolio]

Discovery of the First Selective, Nonpeptidic Orexin 2 Receptor Agonists.

In this issue, Nagase and colleagues report the discovery of the first selective nonpeptidic orexin 2 receptor (OX2R) agonists. The discovery of these OX2R selective agonists opens up new avenues for ...

Design and Synthesis of Non-Peptide, Selective Orexin Receptor 2 Agonists.

Orexins are a family of neuropeptides that regulate sleep/wakefulness, acting on two G protein-coupled receptors, orexin receptors-1 (OX1R) and -2 (OX2R). Genetic and pharmacologic evidence suggests t...

Novel Octahydropyrrolo3,4-cpyrroles are Selective Orexin-2 Antagonists: SAR Leading to a Clinical Candidate.

The pre-clinical characterization of novel octahydropyrrolo[3,4-c]pyrroles that are potent and selective orexin-2 antagonists is described. Optimization of physical and DMPK properties led to the disc...

Involvement of the orexin system in sympathetic nerve regulation.

Orexin, also known as hypocretin, is a secreted neuropeptide implicated in the regulation of sleep and food intake. In the present study, we examined the importance of orexin in regulation of the symp...

Therapeutic potential of 5-HT6 receptor agonists.

Given its predominant expression in the central nervous system (CNS), 5-hydroxytryptamine (5-HT: serotonin) subtype 6 receptor (5-HT6R) has been considered as a valuable target for the development of ...

Clinical Trials [4080 Associated Clinical Trials listed on BioPortfolio]

Measured Hypocretin Levels and Recovery After Hip Surgery

A specific group of neurons in the brain produces hypocretin, a peptide which has been established as an important regulator of sleep and wakefulness. Activation of these neurons (increase...

Postoperative Pain and Angiotensin II Receptor Antagonists

An angiotensin II type 2 receptor (AT2R) antagonist has been assessed for its efficacy in neuropathic pain with promising results. A considerable number of patients undergoing surgery unde...

The Impact of Sleep Disorders on Motor Vehicle Accidents

Patients who have sleep disorders may be involved in accidents more frequently than those without. In addition patients who have sleep disoders may have more serious accidents and have inc...

Gastric pH in Critically Ill Patients

H2-receptor antagonists are the gold standard for stress ulcer prophylaxis in critically ill patients. Various studies demonstrated superiority of proton pump inhibitors over H2-receptor a...

Drug Utilization and Safety Events Among Children Using Esomeprazole, Other Proton Pump Inhibitors or H2-receptor Antagonists

The purpose of this study is 1. To describe patient characteristics and drug usage among children that are prescribed esomeprazole for the first time and to compare them with patie...

Medical and Biotech [MESH] Definitions

Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME.

Conditions characterized by disturbances of usual sleep patterns or behaviors. Sleep disorders may be divided into three major categories: DYSSOMNIAS (i.e. disorders characterized by insomnia or hypersomnia), PARASOMNIAS (abnormal sleep behaviors), and sleep disorders secondary to medical or psychiatric disorders. (From Thorpy, Sleep Disorders Medicine, 1994, p187)

Endogenous compounds and drugs that bind to and activate SEROTONIN RECEPTORS. Many serotonin receptor agonists are used as ANTIDEPRESSANTS; ANXIOLYTICS; and in the treatment of MIGRAINE DISORDERS.

Dyssomnias (i.e., insomnias or hypersomnias) associated with dysfunction of internal sleep mechanisms or secondary to a sleep-related medical disorder (e.g., sleep apnea, post-traumatic sleep disorders, etc.). (From Thorpy, Sleep Disorders Medicine, 1994, p187)

Movements or behaviors associated with sleep, sleep stages, or partial arousals from sleep that may impair sleep maintenance. Parasomnias are generally divided into four groups: arousal disorders, sleep-wake transition disorders, parasomnias of REM sleep, and nonspecific parasomnias. (From Thorpy, Sleep Disorders Medicine, 1994, p191)


Relevant Topics

Women's Health
Latest News Clinical Trials Research Drugs Reports Corporate
Women's Health - key topics include breast cancer, pregnancy, menopause, stroke Follow and track Women's Health News on BioPortfolio: Women's Health News RSS Women'...

Latest News Clinical Trials Research Drugs Reports Corporate
Diabetes Diabetes Endocrine Obesity Oxycontin Renal Disease Thyroid Disorders Endocrinology is the study of the endocrine glands and the hormones that they secrete (Oxford Medical Dictionary). There are several groups of h...

Latest News Clinical Trials Research Drugs Reports Corporate
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...