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).
Zolpidem, sold under the brand name Ambien, among others, is a medication primarily used for the short-term treatment of sleeping problems. Guidelines recommend that it be used only after cognitive behavioral therapy for insomnia and behavioral changes, such as sleep hygiene, have been tried. It decreases the time to sleep onset by about fifteen minutes and at larger doses helps people stay asleep longer. It is taken by mouth and is available in conventional tablets, sublingual tablets, or oral spray.
Zopiclone, sold under the brand name Imovane among others, is a nonbenzodiazepine used to treat difficulty sleeping. Zopiclone is molecularly distinct from benzodiazepine drugs and is classed as a cyclopyrrolone. However, zopiclone increases the normal transmission of the neurotransmitter gamma-aminobutyric acid (GABA) in the central nervous system, via modulating GABAA receptors similarly to the way benzodiazepine drugs do.
Doxepin is a medication used to treat major depressive disorder, anxiety disorders, chronic hives, and trouble sleeping. For hives it is a less preferred alternative to antihistamines. It has a mild to moderate benefit for sleeping problems. It is used as a cream for itchiness due to atopic dermatitis or lichen simplex chronicus.
Brotizolam is a sedative-hypnotic thienotriazolodiazepine drug which is a benzodiazepine analog. It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties, and is considered to be similar in effect to other short-acting hypnotic benzodiazepines such as triazolam or midazolam. It is used in the short-term treatment of severe insomnia. Brotizolam is a highly potent and short-acting hypnotic, with a typical dose ranging from 0.125 to 0.25 milligrams, which is rapidly eliminated with an average half-life of 4.4 hours.
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.
Deramciclane (EGIS-3886) is a non-benzodiazepine-type anxiolytic drug to treat various types of anxiety disorders. Deramciclane is a unique alternative to current anxiolytics on the market because it has a novel chemical structure and target. It acts as an antagonist at the 5-HT2A receptor, as an inverse agonist at the 5-HT2C receptor, and as a GABA reuptake inhibitor. The two serotonin receptors are G protein-coupled receptors and are two of the main excitatory serotonin receptor types. Their excitation has been implicated in anxiety and mood. Deramciclane does not affect CYP3A4 activity in metabolizing other drugs, but it is a weak inhibitor of CYP2D6. Some studies also show the drug to have moderate affinity to dopamine D2 receptors and low affinity to dopamine receptor D1. Researchers are looking for alternatives to benzodiazepines for anxiolytic use because benzodiazepine drugs have sedative and muscle relaxant side effects.
Almorexant (INN; development code ACT-078573) is an orexin antagonist, functioning as a competitive receptor 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.
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.
Vestipitant (INN) is a drug developed by GlaxoSmithKline which acts as a selective antagonist for the NK1 receptor. It is under development as a potential antiemetic and anxiolytic drug, and as a treatment for tinnitus and insomnia.
Suvorexant, sold under the trade name Belsomra, is an orexin antagonist medication for the treatment of insomnia. It is effective for insomnia, at least for four weeks and as compared to a placebo.
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.
TIK-301 (LY-156735) is an agonist for the melatonin receptors MT1 and MT2 that is under development for the treatment of insomnia and other sleep disorders. Its agonist action on MT1 and MT2 receptors in the suprachiasmatic nucleus in the brain enables its action as a chronobiotic. It is in the same class of melatonin receptor agonists as ramelteon and tasimelteon.
Filorexant (INN, USAN) (code name MK-6096) is an orexin antagonist which is or was under development by Merck for the treatment of insomnia. It is a dual antagonist of the OX1 and OX2 receptors. As of March 2014, filorexant has completed phase II clinical trials. It was also investigated as a migraine prophylaxis, but was not found effective, and in major depressive disorder and painful diabetic neuropathy. As of May 2015, filorexant is no longer listed on Merck's online development pipeline.
Seltorexant (former developmental code names MIN-202, JNJ-42847922, JNJ-922) is a selective, small-molecule antagonist of the OX2 receptor that is under development by Minerva Neurosciences and Johnson & Johnson's Janssen Pharmaceuticals for the treatment of insomnia and major depressive disorder (MDD). As of December 2015, it is in phase II clinical trials for both insomnia and major depressive disorder.
Lemborexant, sold under the brand name Dayvigo, is a medication for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance in adults. Lemborexant was approved in the United States for use by adults with insomnia in December 2019.
Daridorexant, sold under the brand name Quviviq, is an orexin antagonist medication that is used for the treatment of insomnia. It is taken by mouth.
Vornorexant (developmental code names ORN-0829, TS-142) is an orexin receptor antagonist which is under development for the treatment of insomnia and sleep apnea syndrome. It is a dual orexin OX1 and OX2 receptor antagonist (DORA). Vornorexant is predicted to have a short elimination half-life in humans, but few clinical data are available so far. As of June 2021, vornorexant is in phase 2 clinical trials for insomnia and phase 1 trials for sleep apnea syndrome.
