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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.
Department of Neuroscience, Merck Research Laboratories, West Point, Pennsylvania, USA.
This article was published in the following journal.
Name: Journal of neurogenetics
Suvorexant is the first dual orexin receptor antagonist for treating insomnia. This study aimed to evaluate the tolerability, efficacy, and safety of suvorexant on insomnia in adolescents.
Orexins ('hypocretins') are peptides produced by neurons of the hypothalamus that project to structures implicated in reward and emotion processing. Converging evidence demonstrates functional roles o...
The orexin/hypocretin system is important for appetitive motivation towards multiple drugs of abuse, including nicotine. Both OX1 and OX2 receptors individually have been shown to influence nicotine s...
Sleep disturbances are associated with type 2 diabetes; therefore, the amelioration of sleep may improve metabolic disorders. To investigate this possibility, we herein examined the effects of suvorex...
Suvorexant is a dual orexin receptor antagonist, recently approved by USFDA for the treatment of insomnia. It is drug-of-abuse and listed in Schedule IV drug of the Controlled Substances Act. In this ...
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 purpose of this study is to examine effects of blocking the orexin system with suvorexant after exposure-based intervention for posttraumatic stress disorder (PTSD) on sleep, PTSD symp...
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...
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...
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...
G-protein-coupled NEUROPEPTIDE RECEPTORS that have specificity for OREXINS and play a role in appetite control, and sleep-wake cycles. Two principle receptor types exist, each having a specificity for OREXIN A and OREXIN B peptide subtypes.
Substances that bind to and inhibit the action of OREXIN RECEPTORS. Drugs in this class have been used as SLEEP AIDS.
A thiazole derivative and atypical ANTIPSYCHOTIC AGENT that functions as a DOPAMINE D2 RECEPTOR ANTAGONIST; SEROTONIN 5-HT2 RECEPTOR ANTAGONIST, serotonin 5-HT7 receptor antagonist, and antagonist of the adrenergic α2A and α2C receptors, as well as a partial SEROTONIN 5-HT1A RECEPTOR AGONIST. It is used in the treatment of SCHIZOPHRENIA and BIPOLAR DISORDER.
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)
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 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...
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