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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 (selective orexin receptor antagonist or SORA) or both (dual orexin receptor antagonist or DORA) 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 * Fazamore ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Orexin
Orexin (), also known as hypocretin, is a neuropeptide that regulates arousal, wakefulness, and appetite. It exists in the forms of orexin-A and orexin-B. The most common form of narcolepsy, type 1, in which the individual experiences brief losses of muscle tone ("drop attacks" or cataplexy), is caused by a lack of orexin in the brain due to destruction of the cells that produce it.Stanford Center for NarcolepsFAQ(retrieved 27-Mar-2012) There are 50,000–80,000 orexin-producing neurons in the human brain, located predominantly in the perifornical area and lateral hypothalamus. They project widely throughout the central nervous system, regulating wakefulness, feeding, and other behaviours. There are two types of orexin peptide and two types of orexin receptor. Orexin was discovered in 1998 almost simultaneously by two independent groups of researchers working on the rat brain. One group named it orexin, from ''orexis,'' meaning "appetite" in Greek; the other group named it hy ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Almorexant
Almorexant (INN), 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. Pharmacology Pharmacodynamics Almorexant is a competitive, dual OX1 and OX2 receptor antagonist and selectively inhibits the functional consequences of OX1 and OX2 receptor activation, such as intracellular Ca2+ mobilization. It dissociates very slowly from the orexin receptors and this may prolong its duration of action. History Originally developed by Actelion, from 2007 almorexant was being reported as a potential blockbuster drug, as its novel mechanism of action (orexin receptor antagonism) was thought to produce better quality sle ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Wake After Sleep Onset
Middle-of-the-night insomnia, or "sleep maintenance insomnia", also called terminal insomnia in contrast with "initial insomnia", is characterized by having difficulty returning to sleep after waking up during the night or very early in the morning. Initial or "sleep-onset" insomnia consists of having difficulty falling asleep at the beginning of sleep. The disrupted sleep patterns caused by middle-of-the-night insomnia make many sufferers of the condition complain of fatigue the following day. Excessive daytime sleepiness is reported nearly two times higher by individuals with nocturnal awakenings than by people who sleep through the night. Sleep research conducted in the 1990s showed that such waking up during the night may be a natural sleep pattern, rather than a form of insomnia. If interrupted sleep (called "biphasic sleeping" or " bimodal sleep") is perceived as normal and not referred to as "insomnia", less distress is caused and a return to sleep usually occurs after ab ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Latency To Persistent Sleep
In sleep science, sleep onset latency (SOL) is the length of time that it takes to accomplish the transition from full wakefulness to sleep, normally to the lightest of the non-REM sleep stages. Sleep latency studies Pioneering Stanford University sleep researcher William C. Dement reports the early development of the concept, and of the first test for it, the Multiple Sleep Latency Test (MSLT), in his book ''The Promise of Sleep''. Dement and colleagues including Mary Carskadon had been seeking an objective measure of daytime sleepiness to help assess the effects of sleep disorders. In the course of evaluating experimental results, they realized that the amount of time it took to fall asleep in bed was closely linked to the subjects' own self-evaluated level of sleepiness. "This may not seem like an earthshaking epiphany, but conceiving and developing an objective measure of sleepiness was perhaps one of the most important advances in sleep science," Dement and coauthor Chris ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dose Dependence
Dose or Dosage may refer to: Music * ''Dose'' (Gov't Mule album), 1998 * ''Dose'' (Latin Playboys album) * ''Dosage'' (album), by the band Collective Soul * "Dose" (song), a 2018 song by Ciara * "Dose", song by Filter from the album '' Short Bus'' Science * Dose (biochemistry), a measured quantity of a medicine, nutrient, or pathogen which is delivered as a unit. * Dosage (pharmacology), prescribed regimen of medication administration, including amount, frequency, and duration * Dosage form, a mixture of active and inactive components used to administer a medication * Dosing, feeding chemicals or medicines when used in small quantities * Effective dose (pharmacology), a dose or concentration of a drug that produces a biological response *Absorbed dose, a measure of energy deposited in matter from ionizing radiation *Equivalent dose, a measure of cancer/heritable health risk in tissue from ionizing radiation *Effective dose (radiation), a measure of cancer/heritable health ri ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
TCS-OX2-29
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 Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ..., with subtype-selective antagonists such as TCS-OX2-29 potentially offering more specificity of action compared to non-selective orexin antagonists like almorexant. References Carboxamides Orexin antagonists Norsalsolinol ethers 4-Pyridyl compounds Sedatives Tert-butyl compounds {{sedative-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SB-408124
SB-408124 is a drug which is a non-peptide antagonist selective for the orexin receptor subtype OX1, with around 70x selectivity for OX1 over 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] |
Anorectic
An anorectic is a drug that reduces appetite, resulting in lower food consumption, leading to weight loss. These substances work by affecting the central nervous system or certain neurotransmitters to create a feeling of fullness or reduce the desire to eat. The understanding of anorexiant effects is crucial in the development of interventions for weight management, eating disorders, and related health concerns. The anorexiant effect can be induced through diverse mechanisms, ranging from hormonal regulation to neural signaling. Ghrelin, leptin, and peptide YY are among the hormones involved in appetite control. Additionally, neurotransmitters such as serotonin and dopamine in the central nervous system contribute significantly to the regulation of food intake. By contrast, an appetite stimulant is referred to as orexigenic. The term is (from the Greek and ), and such drugs are also known as anorexigenic, anorexiant, or appetite suppressant. History Used on a short-term ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sedative
A sedative or tranquilliser is a substance that induces sedation by reducing irritability or Psychomotor agitation, excitement. They are central nervous system (CNS) Depressant, 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, gamma-aminobutyric acid (GABA). Most sedatives produce relaxing effects by increasing GABA activity. This group is related to hypnotics. The term ''sedative'' describes drugs that serve to calm or Anxiolytic, 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. Terminology There is some overlap ... [...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 is a drug that reduces appetite, resulting in lower food consumption, leading to weight loss. These substances work by affecting the central nervous system or certain neurotransmitters to create a feeling of fullness or reduce the desi ... 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 antagonist ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
RTIOX-276
RTIOX-276 is an orexin antagonist. RTIOX-276 binds selectively to the orexin 1 receptor (KE = 8.5nM) and lacks significant affinity for the orexin 2 receptor (KE = > 10,000nM). RTIOX-276 may have therapeutic utility for the treatment of cocaine addiction. In conditioned place preference studies, RTIOX-276 attenuated the development of place preference in mice exposed to cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a .... References Trifluoromethyl compounds Benzylisoquinolines Orexin antagonists 3-Pyridyl compounds Methoxy compounds Acetamides {{Sedative-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
JNJ-10397049
JNJ-10397049 is a potent and highly selective OX2 receptor antagonist. In animals, JNJ-10397049 was found to have sleep-promoting effects and to attenuate the reinforcing effects of ethanol Ethanol (also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound with the chemical formula . It is an Alcohol (chemistry), alcohol, with its formula also written as , or EtOH, where Et is the ps .... References Bromoarenes Dioxanes Orexin antagonists Ureas {{Sedative-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |