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Milameline
Milameline (CI-979, PD-129,409, RU-35,926) is a non-selective muscarinic acetylcholine receptor partial agonist with cognition-acting properties that was being investigated for the treatment of Alzheimer's disease, but produced poor results in clinical trials and was subsequently discontinued. *Changing the ''O''-methyl aldoxime to an ''O''-propargyl oxime instead gives a separate molecule called RU 35986. See also * Alvameline * Sabcomeline * Tazomeline * 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 treatme ... References {{Muscarinic acetylcholine receptor modulators Muscarinic agonists Aldoximes Tetrahydropyridines ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Alvameline
Alvameline (Lu 25-109) is a M1 receptor agonist and M2/ M3 receptor antagonist that was under investigation for the treatment of Alzheimer's disease, but produced poor results in clinical trials and was subsequently discontinued. Synthesis Alkylation of nicotinonitrile (accessible from nicotinamide) (1) with methyl iodide affords the ''N''-methylpyridinium salt (2). The reduction of this intermediate with sodium borohydride gives 3-cyano-''N''-methyl-1,2,5,6- tetrahydropyridine 657-66-9(3). Reaction with ethyl chloroformate results in ''N''-demethylation and consequent formation of the corresponding carbamate 20241-16-9(4). The nitrile group is then transformed to a tetrazole by reaction with sodium azide in the presence of aluminum chloride givinCID:9991151(5). The surrogate acid is then alkylated with ethyl iodide to afforCID:10106197(6). Treatment with acid then removes the carbamate on the ring nitrogen giving Lu-25-077 21549-70-8(7). The methyl group on the pip ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sabcomeline
Sabcomeline (Memric; SB-202,026) is a selective M1 receptor partial agonist that was under development for the treatment of Alzheimer's disease. It made it to phase III clinical trials before being discontinued due to poor results. See also * Alvameline * Milameline * Tazomeline * 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 treatme ... References {{Muscarinic acetylcholine receptor modulators Muscarinic agonists Nitriles Oximes Quinuclidines Experimental drugs ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tazomeline
Tazomeline (LY-287,041) is a drug which acts as a non- selective muscarinic acetylcholine receptor agonist. It was in clinical trials for the treatment of cognitive dysfunction such as that seen in Alzheimer's disease and schizophrenia, but development was apparently scrapped for unknown reasons. Another of the patented uses is for the treatment of "severe painful conditions". Synthesis : A Strecker type alpha-amino nitrile between nicotinaldehyde, potassium cyanide and ammonium chloride gives amino(pyridin-3-yl)acetonitrile 31988-63-1(2). The halogenation of this intermediate with sulfur monochloride 0025-67-9in DMF led to 3-chloro-4-(3-pyridyl)-1,2,5-thiadiazole 31986-28-2(3). : Thioether formation with 1-Hexanethiol 11-31-9(4) in the presence of sodium hydrogen sulfide, DMF and K2CO3 gave 3-(4-hexylthio-1,2,5-thiadiazol-3-yl)pyridineCID:10755149(5). Alkylation with methyl iodide gives 3-(4-hexylthio-1,2,5-thiadiazol-3-yl)-1-methylpyridinium iodideCID:19075299(6). ... [...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] |
Binding Selectivity
Binding selectivity is defined with respect to the binding of ligands to a substrate forming a complex. Binding selectivity describes how a ligand may bind more preferentially to one receptor than another. A selectivity coefficient is the equilibrium constant for the reaction of displacement by one ligand of another ligand in a complex with the substrate. Binding selectivity is of major importance in biochemistry and in chemical separation processes. Selectivity coefficient The concept of selectivity is used to quantify the extent to which one chemical substance, A, binds each of two other chemical substances, B and C. The simplest case is where the complexes formed have 1:1 stoichiometry. Then, the two interactions may be characterized by equilibrium constants ''K''AB and ''K''AC.The constant used here are ''association'' constants. ''Dissociation'' constants are used in some contexts. A dissociation constant is the reciprocal of an association constant. : + B AB; \mathit K_ ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Muscarinic Acetylcholine Receptor
Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-receptor stimulated by acetylcholine released from postganglionic fibers in the parasympathetic nervous system. Muscarinic receptors are so named because they are more sensitive to muscarine than to nicotine. Their counterparts are nicotinic acetylcholine receptors (nAChRs), receptor ion channels that are also important in the autonomic nervous system. Many drugs and other substances (for example pilocarpine and scopolamine) manipulate these two distinct receptors by acting as selective agonists or antagonists. Function Acetylcholine (ACh) is a neurotransmitter found in the brain, neuromuscular junctions and the autonomic ganglia. Muscarinic receptors are used in the following roles: Recovery receptors ACh is always used as the neur ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Partial Agonist
In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonistic effects—when both a full agonist and partial agonist are present, the partial agonist actually acts as a competitive antagonist , competing with the full agonist for receptor occupancy and producing a net decrease in the receptor activation observed with the full agonist alone. Clinically, partial agonists can be used to activate receptors to give a desired submaximal response when inadequate amounts of the endogenous ligand are present, or they can reduce the overstimulation of receptors when excess amounts of the endogenous ligand are present. Some currently common drugs that have been classed as partial agonists at particular receptors include buspirone, aripiprazole, buprenorphine, nalmefene and norclozapine. Examples of ligands acti ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cognition
Cognition refers to "the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought, intelligence, the formation of knowledge, memory and working memory, judgment and evaluation, reasoning and computation, problem solving and decision making, comprehension and production of language. Imagination is also a cognitive process, it is considered as such because it involves thinking about possibilities. Cognitive processes use existing knowledge and discover new knowledge. Cognitive processes are analyzed from different perspectives within different contexts, notably in the fields of linguistics, musicology, anesthesia, neuroscience, psychiatry, psychology, education, philosophy, anthropology, biology, systemics, logic, and computer science. These and other approaches to the analysis of cognition (such as embodied cognition) ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Alzheimer's Disease
Alzheimer's disease (AD) is a neurodegeneration, 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 short-term memory, remembering recent events. As the disease advances, symptoms can include primary progressive aphasia, problems with language, Orientation (mental), disorientation (including easily getting lost), mood swings, loss of motivation, self-neglect, and challenging behaviour, 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 alle ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Clinical Trial
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietary choices, dietary supplements, and medical devices) and known interventions that warrant further study and comparison. Clinical trials generate data on dosage, safety and efficacy. They are conducted only after they have received health authority/ethics committee approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial—their approval does not mean the therapy is 'safe' or effective, only that the trial may be conducted. Depending on product type and development stage, investigators initially enroll volunteers or patients into small pilot studies, and subsequently conduct progressively larger scale comparative studies. Clinical trials can vary i ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Propargyl
In organic chemistry, the propargyl group is a functional group of 2-propynyl with the structure . It is an alkyl group derived from propyne (). The term propargylic refers to a saturated position ( ''sp''3-hybridized) on a molecular framework next to an alkynyl group. The name comes from mix of ''propene'' and ''argentum'', which refers to the typical reaction of the terminal alkynes with silver salts. The term homopropargylic designates in the same manner * a saturated position on a molecular framework next to a propargylic group and thus two bonds from an alkyne moiety. * a 3-butynyl fragment, , or substituted homologue. See also * Alkenyl groups ** Allyl ** Vinyl group * Ethynyl * Propargyl chloride * Propargyl alcohol * Propargyl bromide * Propiolic acid Propiolic acid is the organic compound with the formula HC2CO2H. It is the simplest acetylenic carboxylic acid. It is a colourless liquid that crystallises to give silky crystals. Near its boiling point, it decompo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
RU 35986
''Ru, ru, or RU may refer to: Russia * Russia (ISO 3166-1 alpha-2 country code) * Russian language (ISO 639 alpha-2 code) * .ru, the Internet country code top-level domain for Russia China * Rù (入), the entering tone in Chinese language phonetics * Rú (儒), a Chinese language term for Confucianism * Ru (surname) (茹), a Chinese surname * Ru River (汝), in Henan, China * Ru ware, a type of Chinese pottery Educational institutions * Radboud University Nijmegen, in Nijmegen, Netherlands * Radford University, in Virginia, USA * Rai University in Gujarat, India * Rajshahi University in Bangladesh * Rama University in India * Ramkhamhaeng University in Thailand * Regis University in Colorado, USA * Reykjavík University Iceland * Rhodes University in Grahamstown, South Africa * Rockefeller University in New York, USA * Rockhurst University in Missouri, USA * Roosevelt University in Chicago, Illinois, USA * Rowan University in New Jersey, USA * Ruse University in Bulgari ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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