Hypnotic, or soporific drugs, commonly known as sleeping pills, are a class of psychoactive drugs whose primary function is to induce sleep and to treat insomnia (sleeplessness).
Orexin, also known as hypocretin, is a neuropeptide that regulates arousal, wakefulness, and appetite. The most common form of narcolepsy, type 1, in which the individual experiences brief losses of muscle tone, is caused by a lack of orexin in the brain due to destruction of the cells that produce it. It exists in the forms of Orexin-A and Orexin-B.
Hydroxyzine, sold under the brand names Atarax, Vistaril among others, is an antihistamine medication. It is used in the treatment of itchiness, insomnia, anxiety, and nausea, including that due to motion sickness. It is used either by mouth or injection into a muscle.
Zaleplon, sold under the brand name Sonata among others, is a sedative and hypnotic which is used to treat insomnia. It is a nonbenzodiazepine or Z-drug of the pyrazolopyrimidine class. It was developed by King Pharmaceuticals.
Nonbenzodiazepines, sometimes referred to colloquially as Z-drugs, are a class of psychoactive drugs that are benzodiazepine-like in uses, such as for treating insomnia and anxiety.
Quazepam, sold under brand name Doral among others, is a relatively long-acting benzodiazepine derivative drug developed by the Schering Corporation in the 1970s. Quazepam is used for the treatment of insomnia including sleep induction and sleep maintenance. Quazepam induces impairment of motor function and has relatively selective hypnotic and anticonvulsant properties with considerably less overdose potential than other benzodiazepines. Quazepam is an effective hypnotic which induces and maintains sleep without disruption of the sleep architecture.
SB-649868 is a dual orexin receptor antagonist that was being developed by GlaxoSmithKline as a treatment for insomnia.
The orexin receptor (also referred to as the hypocretin receptor) is a G-protein-coupled receptor that binds the neuropeptide orexin. There are two variants, OX1 and OX2, each encoded by a different gene (HCRTR1, HCRTR2).
Orexin receptor type 1 (Ox1R or OX1), also known as hypocretin receptor type 1 (HcrtR1), is a protein that in humans is encoded by the HCRTR1 gene.
Orexin receptor type 2 (Ox2R or OX2), also known as hypocretin receptor type 2 (HcrtR2), is a protein that in humans is encoded by the HCRTR2 gene.
Almorexant, also known by its development code ACT-078573, is an orexin antagonist, acting as a competitive antagonist of the OX1 and OX2 orexin receptors, which was being developed by the pharmaceutical companies Actelion and GSK for the treatment of insomnia. Development of the drug was abandoned in January 2011 due to concerns over the hepatic safety of almorexant after transient increases in liver enzymes were observed in trials.
TCS-OX2-29 is an orexin antagonist. It was the first non-peptide antagonist developed that is selective for the orexin receptor subtype OX2, with an IC50 of 40nM and selectivity of around 250x for OX2 over OX1 receptors. Orexin antagonists are expected to be useful for the treatment of insomnia, with subtype-selective antagonists such as TCS-OX2-29 potentially offering more specificity of action compared to non-selective orexin antagonists like almorexant.
SB-334867 is an orexin antagonist. It was the first non-peptide antagonist developed that is selective for the orexin receptor subtype OX1, with around 50x selectivity for OX1 over OX2 receptors. It has been shown to produce sedative and anorectic effects in animals, and has been useful in characterising the orexinergic regulation of brain systems involved with appetite and sleep, as well as other physiological processes. The hydrochloride salt of SB-334867 has been demonstrated to be hydrolytically unstable, both in solution and as the solid. Orexin antagonists have multiple potential clinical applications including the treatment of drug addiction, insomnia, obesity and diabetes.
Suvorexant, sold under the brand name Belsomra, is an orexin antagonist medication which is used in the treatment of insomnia. It is indicated specifically for the treatment of insomnia characterized by difficulties with sleep onset and/or maintenance in adults. Suvorexant helps with falling asleep faster, sleeping longer, being awake less in the middle of the night, and having better quality of sleep. Its effectiveness is modest, and is similar to that of other orexin antagonists, but is lower than that of benzodiazepines and Z-drugs. Suvorexant is taken by mouth.
An orexin receptor antagonist, or orexin antagonist, is a drug that inhibits the effect of orexin by acting as a receptor antagonist of one or both of the orexin receptors, OX1 and OX2. Medical applications include treatment of sleep disorders such as insomnia.
Filorexant (INN, USAN; developmental code name MK-6096) is an orexin antagonist which was under development by Merck for the treatment of insomnia, depression, diabetic neuropathy, and migraine. It is a dual antagonist of the orexin OX1 and OX2 receptors. It has a relatively short elimination half-life of 3 to 6 hours. However, it dissociates slowly from the orexin receptors and may thereby have a longer duration. Possibly in relation to this, filorexant shows next-day somnolence similarly to suvorexant. In phase 2 clinical trials, filorexant was found to be effective in the treatment of insomnia, but was not effective in the treatment of major depressive disorder, painful diabetic neuropathy, or migraine. As of May 2015, filorexant was no longer listed on Merck's online development pipeline and hence development of the drug appears to have been discontinued. Development of filorexant may have been discontinued due to lack of differentiation from suvorexant (which was also developed by Merck).
Seltorexant, also known by its developmental code names MIN-202 and JNJ-42847922, is an orexin antagonist medication which is under development for the treatment of depression and insomnia. It is a selective antagonist of the orexin OX2 receptor (2-SORA). The medication is taken by mouth. As of February 2022, seltorexant is in phase 3 clinical trials for treatment of major depressive disorder (MDD) and phase 2 trials for treatment of insomnia. It was also under investigation for the treatment of sleep apnea, but no recent development has been reported for this indication. Seltorexant is under development by Minerva Neurosciences and Johnson & Johnson's Janssen Pharmaceuticals.
Lemborexant, sold under the brand name Dayvigo, is an orexin antagonist medication which is used in the treatment of insomnia. It is indicated specifically for the treatment of insomnia characterized by difficulties with sleep onset and/or maintenance in adults. The medication is taken by mouth.
Daridorexant, sold under the brand name Quviviq, is an orexin antagonist medication which is used for the treatment of insomnia. Daridorexant is taken by mouth.
Vornorexant, also known by its developmental code names ORN-0829 and TS-142, is an orexin antagonist medication which is under development for the treatment of insomnia and sleep apnea. It is a dual orexin OX1 and OX2 receptor antagonist (DORA). The medication is taken by mouth. As of June 2021, vornorexant is in phase 2 clinical trials for insomnia and phase 1 trials for sleep apnea. It is under development by Taisho Pharmaceutical.
