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KarXT
KarXT is an investigational oral dual-drug fixed-dose combination of xanomeline and trospium. It is undergoing a phase 3 clinical trial for the treatment of patients suffering from the symptoms of schizophrenia. Xanomeline is a functionally preferring muscarinic M4 and M1 receptor agonist that readily passes into the central nervous system (CNS) to stimulate these receptors in key areas of the brain. Trospium is a non-selective muscarinic antagonist that does not cross into the CNS and reduces peripheral cholinergic side effects associated with xanomeline. Mechanism of action Preclinical data supports the hypothesis that xanomeline’s central mechanism of action is mediated primarily through stimulation of brain muscarinic M4 and M1 receptors. M4 muscarinic receptors are most highly expressed in the midbrain, which controls motor and action planning, decision-making, motivation, reinforcement, and reward perception. M1 muscarinic receptors are most highly expressed in the cer ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Xanomeline
Xanomeline (LY-246,708; Lumeron, Memcor) is a small molecule muscarinic acetylcholine receptor agonist that was first synthesized in a collaboration between Eli Lilly and Novo Nordisk as an investigational therapeutic being studied for the treatment of central nervous system disorders. Its pharmacological action is mediated primarily through stimulation of central nervous system muscarinic M1 and M4 receptor subtypes. Xanomeline is currently being developed as a combination drug (Kar-XT; xanomeline + trospium) by Karuna Therapeutics. Trospium is a non-CNS penetrant non-selective muscarinic antagonist to quell peripheral muscarinic agonist-dependent side effects. Xanomeline’s mechanism of action is hypothesized to be via rebalancing key neurotransmitter circuits, including acetylcholine, dopamine, and glutamate, which are disrupted in schizophrenia and related diseases. Chemistry Xanomeline has structural and pharmacological similarities to the main psychoactive ingredient ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
5-HT2A Receptor
The 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor (GPCR). The 5-HT2A receptor is a cell surface receptor, but has several intracellular locations. 5-HT is short for 5-hydroxy-tryptamine or serotonin. This is the main excitatory receptor subtype among the GPCRs for serotonin, although 5-HT2A may also have an inhibitory effect on certain areas such as the visual cortex and the orbitofrontal cortex. This receptor was first noted for its importance as a target of serotonergic psychedelic drugs such as LSD and psilocybin mushrooms. Later it came back to prominence because it was also found to be mediating, at least partly, the action of many antipsychotic drugs, especially the atypical ones. Downregulation of post-synaptic 5-HT2A receptor is an adaptive process provoked by chronic administration of selective serotonin reuptake inhibitors (SSRIs) and atypical antipsychotics. Suicidal and otherwis ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Novo Nordisk
Novo Nordisk A/S is a Danish multinational pharmaceutical company headquartered in Bagsværd, Denmark, with production facilities in nine countries, and affiliates or offices in five countries. Novo Nordisk is controlled by majority shareholder Novo Holdings A/S which holds approximately 25% of its shares and a supermajority (45%) of its voting shares. Novo Nordisk manufactures and markets pharmaceutical products and services specifically diabetes care medications and devices. Novo Nordisk is also involved with hemostasis management, growth hormone therapy and hormone replacement therapy. The company makes several drugs under various brand names, including Levemir, Tresiba, NovoLog, Novolin R, NovoSeven, NovoEight and Victoza. Novo Nordisk employs more than 48,000 people globally, and markets its products in 168 countries. The corporation was created in 1989 through a merger of two Danish companies which date back to the 1920s. The Novo Nordisk logo is the Apis bull, one of t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Eli Lilly
Eli Lilly (July 8, 1838 – June 6, 1898) was an American soldier, pharmacist, chemist, and businessman who founded the Eli Lilly and Company pharmaceutical corporation. Lilly enlisted in the Union Army during the American Civil War and recruited a company of men to serve with him in the 18th Independent Battery Indiana Light Artillery. He was later promoted to Major (United States), major and then colonel, and was given command of the 9th Regiment Indiana Cavalry. Lilly was captured in September 1864 and held as a prisoner of war until January 1865. After the war, he attempted to run a plantations in the American South, plantation in Mississippi, but it failed and he returned to his pharmacy profession after the death of his first wife. Lilly remarried and worked with business partners in several pharmacies in Indiana and Illinois before opening his own business in 1876 in Indianapolis. Lilly's company manufactured drugs and marketed them on a wholesale basis to pharmacies ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Psychosis
Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior that is inappropriate for a given situation. There may also be sleep problems, social withdrawal, lack of motivation, and difficulties carrying out daily activities. Psychosis can have serious adverse outcomes. As with many psychiatric phenomena, psychosis has several different causes. These include mental illness, such as schizophrenia or schizoaffective disorder, bipolar disorder, sensory deprivation and in rare cases, major depression (psychotic depression). Other causes include: trauma, sleep deprivation, some medical conditions, certain medications, and drugs such as cannabis, hallucinogens, and stimulants. One type, known as postpartum psychosis, can occur after giving birth. The neurotransmitter dopamine is believed to p ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Alzheimer’s Disease
Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems with language, disorientation (including easily getting lost), mood swings, loss of motivation, self-neglect, and behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the typical life expectancy following diagnosis is three to nine years. The cause of Alzheimer's disease is poorly understood. There are many environmental and genetic risk factors associated with its development. The strongest genetic risk factor is from an allele of APOE. Other risk factors include a history of head injury, clinical depression, and high blood pressu ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Glutamatergic
Glutamatergic means "related to glutamate". A glutamatergic agent (or drug) is a chemical that directly modulates the excitatory amino acid (glutamate/ aspartate) system in the body or brain. Examples include excitatory amino acid receptor agonists, excitatory amino acid receptor antagonists, and excitatory amino acid reuptake inhibitors. See also * Adenosinergic * Adrenergic * Cannabinoidergic * Cholinergic * Dopaminergic * GABAergic * GHBergic * Glycinergic * Histaminergic * Melatonergic * Monoaminergic * Opioidergic * Serotonergic * Sigmaergic Sigma receptors (σ-receptors) are protein cell surface receptors that bind ligands such as 4-PPBP (4-phenyl-1-(4-phenylbutyl) piperidine), SA 4503 (cutamesine), ditolylguanidine, dimethyltryptamine, and siramesine. There are two subtypes, ... References Neurochemistry Neurotransmitters {{nervous-system-drug-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dopaminergic
Dopaminergic means "related to dopamine" (literally, "working on dopamine"), dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic brain pathways facilitate dopamine-related activity. For example, certain proteins such as the dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and dopamine receptors can be classified as dopaminergic, and neurons that synthesize or contain dopamine and synapses with dopamine receptors in them may also be labeled as ''dopaminergic''. Enzymes that regulate the biosynthesis or metabolism of dopamine such as aromatic L-amino acid decarboxylase or DOPA decarboxylase, monoamine oxidase (MAO), and catechol ''O''-methyl transferase (COMT) may be referred to as ''dopaminergic'' as well. Also, any endogenous or exogenous chemical substance that acts to affect dopamine receptors or dopamine release through indirect actions (for example, on neurons t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Serotonin
Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vasoconstriction. Approximately 90% of the serotonin that the body produces is in the intestinal tract. Biochemically, the indoleamine molecule derives from the amino acid tryptophan, via the (rate-limiting) hydroxylation of the 5 position on the ring (forming the intermediate 5-hydroxytryptophan), and then decarboxylation to produce serotonin. Serotonin is primarily found in the enteric nervous system located in the gastrointestinal tract (GI tract). However, it is also produced in the central nervous system (CNS), specifically in the raphe nuclei located in the brainstem, Merkel cells located in the skin, pulmonary neuroendocrine cells and taste receptor cells in the tongue. Additionally, serotonin is stored in blood platelets and is ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Trospium Chloride
Trospium chloride is used to treat overactive bladder.UK eMRegurin XL 60mgLast updated July 3, 2015 It has side effects typical of drugs like it, namely dry mouth, stomach upset, and constipation; these side effects cause problems with people taking their medicine as directed. However it doesn't cause central nervous system side effects like other drugs of its class. It is pregnancy category C and is excreted somewhat in breast milk.FDTrospium chloride labelLast updated January 2011 Chemically it is a quaternary ammonium cation which causes it to stay in periphery rather than crossing the blood–brain barrier. It works by causing the smooth muscle in the bladder to relax. It was patented in 1966 and approved for medical use in 1974. It was first approved in the US in 2004, and an extended release version with once-daily dosing was brought to market in 2007. It became generic in Europe in 2009 and in the US the first extended-release generic was approved in 2012. Medic ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dopamine Receptor D2
Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the ''DRD2'' gene. After work from Paul Greengard's lab had suggested that dopamine receptors were the site of action of antipsychotic drugs, several groups, including those of Solomon Snyder and Philip Seeman used a radiolabeled antipsychotic drug to identify what is now known as the dopamine D2 receptor. The dopamine D2 receptor is the main receptor for most antipsychotic drugs. The structure of DRD2 in complex with the atypical antipsychotic risperidone has been determined. Function D2 receptors are coupled to Gi subtype of G protein. This G protein-coupled receptor inhibits adenylyl cyclase activity. In mice, regulation of D2R surface expression by the neuronal calcium sensor-1 (NCS-1) in the dentate gyrus is involved in exploration, synaptic plasticity and memory formation. Studies have shown potential roles for D2R in retrieval of fear memories in the prelimbic cortex and in discrimina ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cerebral Cortex
The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting of allocortex. It is separated into two cortices, by the longitudinal fissure that divides the cerebrum into the left and right cerebral hemispheres. The two hemispheres are joined beneath the cortex by the corpus callosum. The cerebral cortex is the largest site of neural integration in the central nervous system. It plays a key role in attention, perception, awareness, thought, memory, language, and consciousness. The cerebral cortex is part of the brain responsible for cognition. In most mammals, apart from small mammals that have small brains, the cerebral cortex is folded, providing a greater surface area in the confined volume of the cranium. Apart from minimising brain and cranial volume, cortical folding is crucial for the brain ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
