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

17:39 EST 3rd March 2015 | 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.

Affiliation

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
Pages:

Links

PubMed Articles [27595 Associated PubMed Articles listed on BioPortfolio]

Therapeutic Effects of Melatonin Receptor Agonists on Sleep and Comorbid Disorders.

Several melatonin receptors agonists (ramelteon, prolonged-release melatonin, agomelatine and tasimelteon) have recently become available for the treatment of insomnia, depression and circadian rhythm...

OX1 and OX2 orexin/hypocretin receptor pharmacogenetics.

Orexin/hypocretin peptide mutations are rare in humans. Even though human narcolepsy is associated with orexin deficiency, this is only extremely rarely due to mutations in the gene coding prepro-orex...

Wen-dan decoction improves negative emotions in sleep-deprived rats by regulating orexin-a and leptin expression.

Wen-Dan Decoction (WDD), a formula of traditional Chinese medicine, has been clinically used for treating insomnia for approximately 800 years. However, the therapeutic mechanisms of WDD remain unclea...

GABAA receptor-mediated input change on orexin neurons following sleep deprivation.

Orexins are bioactive peptides, which have been shown to play a pivotal role in vigilance state transitions: the loss of orexin-producing neurons (orexin neurons) leads to narcolepsy with cataplexy in...

New treatments for headache.

Migraine and cluster headache are primary headache disorders commonly encountered in clinical practice. Despite the profound disability caused by these primary headache disorders, available acute and ...

Clinical Trials [3452 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...

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...

Effectiveness of GABA Agonists in Reducing the Reinforcing Effects of Cocaine

Cocaine abuse continues to represent a significant public-health concern. Cocaine likely creates its addictive effects by increasing levels of dopamine, a chemical found in the brain. GABA...

Ramosetron, Aprepitant and Dexamethasone (RAD) in Solid Cancer

Cisplatin is one of the most emetogenic drugs used in clinical practice and it could result in poor compliance with chemotherapy. The 5-HT3 receptor antagonists prevent vomiting in acute p...

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)

Search BioPortfolio:
Loading
Advertisement

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'...

Endocrinology
Latest News Clinical Trials Research Drugs Reports Corporate
Endocrinology is the study of the endocrine glands and the hormones that they secrete (Oxford Medical Dictionary). There are several groups of hormones; Reproductive/Sex hormones such as FSH, LH, Oestrogen and Testosterone can affect fertility, se...

Advertisement