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SB-408124
SB-408124 is a drug which is a non-peptide antagonist selective for the orexin receptor subtype Hypocretin (orexin) receptor 1, OX1, with around 70x selectivity for OX1 over Hypocretin (orexin) receptor 2, OX2 receptors, and improved oral bioavailability compared to the older OX1 antagonist SB-334867. It is used in scientific research into the function of orexinergic neurons in the body. References Orexin antagonists Fluoroarenes Quinolines Sedatives Ureas {{sedative-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Orexin Receptor
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 (, ). Both orexin receptors exhibit a similar pharmacology – the 2 orexin peptides, orexin-A and orexin-B, bind to both receptors and, in each case, agonist binding results in an increase in intracellular calcium levels. However, orexin-B shows a 5- to 10-fold selectivity for orexin receptor type 2, whilst orexin-A is equipotent at both receptors. Several orexin receptor antagonists are in development for potential use in sleep disorders. The first of these, suvorexant, has been on the market in the United States since 2015. There were two orexin agonists under development . Ligands Several drugs acting on the orexin system are under development, either orexin agonists for the treatment of conditions such as narcolepsy, or orexin antagonists for insomnia. In August 2015 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Orexin Antagonists
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. Examples Marketed * Daridorexant (nemorexant; Quviviq) – dual OX1 and OX2 antagonist – approved for insomnia in January 2022, formerly under development for sleep apnea – half-life 8 hours * Lemborexant (Dayvigo) – dual OX1 and OX2 antagonist – approved for insomnia in December 2019 and released June 1 2020, under development for circadian rhythm sleep disorders, chronic obstructive pulmonary disease, and sleep apnea – half-life 17–55 hours * Suvorexant (Belsomra) – dual OX1 and OX2 antagonist – approved for insomnia in August 2014, under development for delirium – half-life 12 hours Under development * Seltorexant (MIN-202, JNJ-42847922, JNJ-922) – selective OX2 antagonist – under development fo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hypocretin (orexin) Receptor 1
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. Function The orexin 1 receptor (OX1), is a G-protein coupled receptor that is heavily expressed in projections from the lateral hypothalamus and is involved in the regulation of feeding behaviour. OX1 selectively binds the orexin-A neuropeptide. It shares 64% identity with Hypocretin (orexin) receptor 2, OX2. Ligands Agonists * Orexin-A Antagonists * RTIOX-276 - Selective OX1 antagonist * ACT-335827 - Selective OX1 antagonist * Almorexant - Dual OX1 and Hypocretin (orexin) receptor 2, OX2 receptor antagonist, antagonist * Lemborexant - Dual OX1 and Hypocretin (orexin) receptor 2, OX2 receptor antagonist, antagonist * Nemorexant - Dual OX1 and OX2 antagonist * SB-334,867 - Selective OX1 antagonist * SB-408,124 - Selective OX1 antagonist * SB-649,868 - Dual OX1 and Hypocretin (orexin) receptor 2, OX2 receptor antagonist, antagon ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hypocretin (orexin) Receptor 2
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. Structure The structure of the receptor has been solved to 2.5 Å resolution as a fusion protein bound to suvorexant using lipid-mediated crystallization. Function OX2 is a G-protein coupled receptor expressed exclusively in the brain. It has 64% identity with OX1. OX2 binds both orexin A and orexin B neuropeptides. OX2 is involved in the central feedback mechanism that regulates feeding behaviour. Mice with enhanced OX2 signaling are resistant to high-fat diet-induced obesity. This receptor is activated by Hipocretin, which is a wake-promoting hypothalamic neuropeptide that acts as a critical regulator of sleep in animals as Zebrafish or Mammals. This protein has mutations in Astyanax mexicanus that reduces the sleep needs of the cavefish. Ligands Agonists * Danavorexton (TAK-925) – selective OX2 receptor agonist * ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SB-334867
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 An anorectic or anorexic is a drug which reduces appetite, resulting in lower food consumption, leading to weight loss. By contrast, an appetite stimulant is referred to as orexigenic. The term is (from the Greek ''ἀν-'' (an-) = "without" a ... 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. References Sedatives Orexin antagonists ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Quinolines
Quinoline is a heterocyclic aromatic organic compound with the chemical formula C9H7N. It is a colorless hygroscopic liquid with a strong odor. Aged samples, especially if exposed to light, become yellow and later brown. Quinoline is only slightly soluble in cold water but dissolves readily in hot water and most organic solvents. Quinoline itself has few applications, but many of its derivatives are useful in diverse applications. A prominent example is quinine, an alkaloid found in plants. Over 200 biologically active quinoline and quinazoline alkaloids are identified. 4-Hydroxy-2-alkylquinolines (HAQs) are involved in antibiotic resistance. Occurrence and isolation Quinoline was first extracted from coal tar in 1834 by German chemist Friedlieb Ferdinand Runge; he called quinoline ''leukol'' ("white oil" in Greek). Coal tar remains the principal source of commercial quinoline. In 1842, French chemist Charles Gerhardt obtained a compound by dry distilling quinine, str ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sedatives
A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but the majority of them affect the neurotransmitter gamma-aminobutyric acid (GABA). In spite of the fact that each sedative acts in its own way, most produce relaxing effects by increasing GABA activity. This group is related to hypnotics. The term ''sedative'' describes drugs that serve to calm or relieve anxiety, whereas the term ''hypnotic'' describes drugs whose main purpose is to initiate, sustain, or lengthen sleep. Because these two functions frequently overlap, and because drugs in this class generally produce dose-dependent effects (ranging from anxiolysis to loss of consciousness) they are often referred to collectively as ''sedative-hypnotic'' drugs. Sedatives can be used to produce an overly-calming effect (alcohol being the most ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
