Advertisement

Topics

Promotion of Sleep by Suvorexant-A Novel Dual Orexin Receptor Antagonist.

06:00 EDT 9th April 2011 | BioPortfolio

Summary of "Promotion of Sleep by Suvorexant-A Novel Dual Orexin Receptor Antagonist."

Abstract: Orexins/hypocretins are key neuropeptides responsible for regulating central arousal and reward circuits. Two receptors respond to orexin signaling, orexin 1 receptor (OX(1)R) and orexin 2 receptor (OX(2)R) with partially overlapping nervous system distributions. Genetic studies suggest orexin receptor antagonists could be therapeutic for insomnia and other disorders with disruptions of sleep and wake. Suvorexant (MK-4305) is a potent, selective, and orally bioavailable antagonist of OX(1)R and OX(2)R currently under clinical investigation as a novel therapy for insomnia. Examination of Suvorexant in radioligand binding assays using tissue from transgenic rats expressing the human OX(2)R found nearly full receptor occupancy (>90%) at plasma exposures of 1.1 μM. Dosed orally Suvorexant significantly and dose-dependently reduced locomotor activity and promoted sleep in rats (10, 30, and 100 mg/kg), dogs (1 and 3 mg/kg), and rhesus monkeys (10 mg/kg). Consistent cross-species sleep/wake architecture changes produced by Suvorexant highlight a unique opportunity to develop dual orexin antagonists as a novel therapy for insomnia.

Affiliation

Department of Neuroscience, Merck Research Laboratories, West Point, Pennsylvania, USA.

Journal Details

This article was published in the following journal.

Name: Journal of neurogenetics
ISSN: 1563-5260
Pages:

Links

DeepDyve research library

PubMed Articles [10210 Associated PubMed Articles listed on BioPortfolio]

On-the-road driving performance the morning after bedtime use of suvorexant 15 and 30 mg in healthy elderly.

Suvorexant is a first-in-class orexin receptor antagonist for treating insomnia. There is a general concern that hypnotics may impair next-morning driving ability.

Assessment of the Abuse Potential of the Orexin Receptor Antagonist, Suvorexant, Compared With Zolpidem in a Randomized Crossover Study.

Suvorexant is a dual orexin receptor antagonist approved in the United States and Japan for the treatment of insomnia at a maximum dose of 20 mg. This randomized double-blind crossover study evaluated...

Hypothalamic orexin's role in exacerbated cutaneous vasodilation responses to an anxiogenic stimulus in a surgical menopause model.

Distressing symptoms such as hot flashes and sleep disturbances affect over 70% of women approaching menopause for an average of 4-7 years, and recent large cohort studies have shown that anxiety and ...

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 ...

Orexin-A stimulates the expression of GLUT4 in a glucose dependent manner in the liver of orange-spotted grouper (Epinephelus coioides).

Orexins are hypothalamic neuropeptides involved in the central regulation of feeding behavior, sleep-wake cycle and other physiological functions. Orexin-A can regulate energy metabolism and increase ...

Clinical Trials [3504 Associated Clinical Trials listed on BioPortfolio]

Role of the Orexin Receptor System in Stress, Sleep and Cocaine Use

The purpose of this study is to determine the effectiveness of a medication called suvorexant in reducing anxiety, improving sleep, and reducing cocaine cravings or cocaine use.

The Role of Orexin in Human Panic Disorder

The purpose of this study is to provide some information (pilot data) about whether the study drug, suvorexant, (1) affects levels of orexin in people with panic disorder, and (2) is assoc...

Examination of the Effectiveness of Suvorexant in Improving Daytime Sleep in Shift Workers

The purpose of this study is to test the hypothesis that ingestion of the wake-inhibiting drug suvorexant 30 minutes prior to daytime sleep initiation in individuals working overnight shif...

Safety and Efficacy of Suvorexant (MK-4305) for the Treatment of Insomnia in Participants With Alzheimer's Disease (MK-4305-061)

This study aims to examine the safety and efficacy of suvorexant (MK-4305) to improve sleep in individuals with Alzheimer's disease (AD). The primary hypothesis for the study is that suvor...

Suvorexant in Insomnia Co-morbid With Fibromyalgia

This study will compare sleep, pain and daytime sleepiness/fatigue in people with insomnia co-morbid with fibromyalgia while treated short-term with suvorexant 20 mg versus placebo.

Medical and Biotech [MESH] Definitions

Periods of sleep manifested by changes in EEG activity and certain behavioral correlates; includes Stage 1: sleep onset, drowsy sleep; Stage 2: light sleep; Stages 3 and 4: delta sleep, light sleep, deep sleep, telencephalic sleep.

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)

A sleep disorder of central nervous system origin characterized by prolonged nocturnal sleep and periods of daytime drowsiness. Affected individuals experience difficulty with awakening in the morning and may have associated sleep drunkenness, automatic behaviors, and memory disturbances. This condition differs from narcolepsy in that daytime sleep periods are longer, there is no association with CATAPLEXY, and the multiple sleep latency onset test does not record sleep-onset rapid eye movement sleep. (From Chokroverty, Sleep Disorders Medicine, 1994, pp319-20; Psychiatry Clin Neurosci 1998 Apr:52(2):125-129)

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)

Quick Search
Advertisement
 


DeepDyve research library

Relevant Topics

Sleep Disorders
Sleep disorders disrupt sleep during the night, or cause sleepiness during the day, caused by physiological or psychological factors. The common ones include snoring and sleep apnea, insomnia, parasomnias, sleep paralysis, restless legs syndrome, circa...

Blood
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells.  In vertebrates, it is composed of blo...

The Top 100 Pharmaceutical Companies
Top 10 biotech and pharmaceutical companies worldwide based on market value in 2015 2015 ranking of the global top 10 biotech and pharmaceutical companies based on revenue (in billion U.S. dollars) Johnson & Johnson, U.S. 74...