|
Dipraglurant
Dipraglurant ( INN; development code ADX-48621) is a negative allosteric modulator of the mGlu5 receptor which is under development by Addex Therapeutics for the treatment of Parkinson's disease levodopa-induced dyskinesia (PD-LID). As of 2014, it is in phase II clinical trials for this indication. Addex Therapeutics is also investigating an extended-release formulation of dipraglurant for the treatment of non- parkinsonian dystonia Dystonia is a neurology, neurological Hyperkinesia, hyperkinetic Movement disorders, movement disorder in which sustained or repetitive muscle contractions occur involuntarily, resulting in twisting and repetitive movements or abnormal fixed po .... See also * Basimglurant * Fenobam * Mavoglurant * Raseglurant References External links Dipraglurant-IR for Parkinson's disease levodopa-induced dyskinesia - Addex Therapeutics Dipraglurant-ER for dystonia - Addex Therapeutics Alkyne derivatives Antidyskinetic agents Glutamate receptor ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Negative Allosteric Modulator
In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimuli. Some of them, like benzodiazepines or alcohol, function as psychoactive drugs. The site that an allosteric modulator binds to (i.e., an ''allosteric site'') is not the same one to which an endogenous agonist of the receptor would bind (i.e., an ''orthosteric site''). Modulators and agonists can both be called receptor ligands. Allosteric modulators can be 1 of 3 types either: positive, negative or neutral. Positive types increase the response of the receptor by increasing the probability that an agonist will bind to a receptor (i.e. affinity), increasing its ability to activate the receptor (i.e. efficacy), or both. Negative types decrease the agonist affinity and/or efficacy. Neutral types don't affect agonist activity but can stop other modulators from binding to an allosteric site. Some modulators also work as allosteric agonist ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Imidazopyridines
An imidazopyridine is a nitrogen containing heterocycle that is also a class of drugs that contain this same chemical substructure. In general, they are GABAA receptor agonists, however recently proton pump inhibitors, aromatase inhibitors, NSAIDs and other classes of drugs in this class have been developed as well. Despite usually being similar to them in effect, they are not chemically related to benzodiazepines. As such, GABAA-agonizing imidazopyridines, pyrazolopyrimidines, and cyclopyrrones are sometimes grouped together and referred to as "nonbenzodiazepines." Imidazopyridines include: Sedatives Anxiolytics, sedatives and hypnotics ( GABAA receptor positive allosteric modulators): * Imidazo,2-ayridines: ** Alpidem (original brand name Ananxyl)—an anxiolytic that was withdrawn from the market worldwide in 1995 due to hepatotoxicity. ** DS-1—a GABAA receptor positive allosteric modulator selective for the α4 β3 δ subtype, which is not targeted by other GABAer ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Glutamate Receptor Negative Allosteric Modulators
Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synthesize enough for its use. It is also the most abundant excitatory neurotransmitter in the vertebrate nervous system. It serves as the precursor for the synthesis of the inhibitory gamma-aminobutyric acid (GABA) in GABAergic neurons. Its molecular formula is . Glutamic acid exists in two optically isomeric forms; the dextrorotatory -form is usually obtained by hydrolysis of gluten or from the waste waters of beet-sugar manufacture or by fermentation.Webster's Third New International Dictionary of the English Language Unabridged, Third Edition, 1971. Its molecular structure could be idealized as HOOC−CH()−()2−COOH, with two carboxyl groups −COOH and one amino group −. However, in the solid state and mildly acidic water solution ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Antidyskinetic Agents
Dyskinesia refers to a category of movement disorders that are characterized by involuntary muscle movements, including movements similar to tics or chorea and diminished voluntary movements. Dyskinesia can be anything from a slight tremor of the hands to an uncontrollable movement of the upper body or lower extremities. Discoordination can also occur internally especially with the respiratory muscles and it often goes unrecognized. Dyskinesia is a symptom of several medical disorders that are distinguished by their underlying causes. Types Medication-induced dyskinesias Acute dystonia is a sustained muscle contraction that sometimes appears soon after administration of antipsychotic medications. Any muscle in the body may be affected, including the jaw, tongue, throat, arms, or legs. When the throat muscles are involved, this type of dystonia is called an acute laryngospasm and is a medical emergency because it can impair breathing. Older antipsychotics such as haloperidol or fl ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Alkyne Derivatives
\ce \ce Acetylene \ce \ce \ce Propyne \ce \ce \ce \ce 1-Butyne In organic chemistry, an alkyne is an unsaturated hydrocarbon containing at least one carbon—carbon triple bond. The simplest acyclic alkynes with only one triple bond and no other functional groups form a homologous series with the general chemical formula . Alkynes are traditionally known as acetylenes, although the name ''acetylene'' also refers specifically to , known formally as ethyne using IUPAC nomenclature. Like other hydrocarbons, alkynes are generally hydrophobic. Structure and bonding In acetylene, the H–C≡C bond angles are 180°. By virtue of this bond angle, alkynes are rod-like. Correspondingly, cyclic alkynes are rare. Benzyne cannot be isolated. The C≡C bond distance of 118 picometers (for C2H2) is much shorter than the C=C distance in alkenes (132 pm, for C2H4) or the C–C bond in alkanes (153 pm). : The triple bond is very strong with a bond strength of 839 kJ/mol. The si ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Raseglurant
Raseglurant ( INN) (code name ADX-10059) is a negative allosteric modulator of the mGlu5 receptor and derivative of MPEP which was under development by Addex Therapeutics for the treatment of migraine, gastroesophageal reflux disease, and dental anxiety. It reached phase II clinical trials for all of the aforementioned indications before being discontinued due to the observation of possible predictive signs of hepatotoxicity in patients with long-term use. See also * Basimglurant * Dipraglurant Dipraglurant ( INN; development code ADX-48621) is a negative allosteric modulator of the mGlu5 receptor which is under development by Addex Therapeutics for the treatment of Parkinson's disease levodopa-induced dyskinesia (PD-LID). As of 2014, ... * Fenobam * Mavoglurant References External links Development of ADX10059 Ended for Long-term Use - Addex Therapeutics MGlu5 receptor antagonists 3-Fluorophenyl compounds 3-Aminopyridines Alkyne derivatives Glutamate recept ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mavoglurant
Mavoglurant (developmental code name AFQ-056) is an experimental drug candidate for the treatment of fragile X syndrome and other conditions. It exerts its effect as an antagonist of the metabotropic glutamate receptor 5 (mGluR5). Mavoglurant was under development by Novartis and reached phase II and phase III clinical trials. Phase IIb/III dose finding and evaluation trials for fragile X-syndrome were discontinued by the end of 2014. Otherwise, it would have been the first drug to treat the underlying disorder instead of the symptoms of fragile X syndrome. Mavoglurant was also in phase II clinical trials for Levodopa-induced dyskinesia. In 2007, Norvartis had conducted a clinical study to assess its ability of reducing cigarette smoking, but no results had been published up till now. Novartis was conducting a clinical trial with this drug on obsessive–compulsive disorder. Novartis discontinued development of mavoglurant for fragile X syndrome in April 2014 following disappoint ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Fenobam
Fenobam is an imidazole derivative developed by McNeil Laboratories in the late 1970s as a novel anxiolytic drug with an at-the-time-unidentified molecular target in the brain. Subsequently, it was determined that fenobam acts as a potent and selective negative allosteric modulator of the metabotropic glutamate receptor subtype mGluR5, and it has been used as a lead compound for the development of a range of newer mGluR5 antagonists. Fenobam has anxiolytic effects comparable to those of benzodiazepine drugs, but was never commercially marketed for the treatment of anxiety due to dose-limiting side effects such as amnesia and psychotomimetic symptoms. Following the discovery of its activity as a potent negative allosteric modulator of mGluR5, fenobam has been re-investigated for many applications, with its profile of combined antidepressant, anxiolytic, analgesic and anti-addictive effects potentially useful given the common co-morbidity of these symptoms. It has also shown promi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Basimglurant
Basimglurant (INN; developmental code RG-7090 and RO-4917523) is a negative allosteric modulator of the mGlu5 receptor which is under development by Roche and Chugai Pharmaceutical for the treatment of treatment-resistant depression (as an adjunct) and fragile X syndrome. As of November 2016, it has undergone phase II clinical trials for both of these indications. It was discovered in a medicinal chemistry effort conducted at Roche starting from the results of a small molecular weight compound library high-throughput screen based on a Ca21 mobilization assay with human mGlu5a (Jaeschke et al., 2015). The high-throughput screen identified several mGlu5 antagonists such as MPEP, MTEP, and fenobam. In partnership with Chugai Pharmaceutical, basimglurant is currently still undergoing revision from previous drug trials as of November 2016. Pharmacology Mechanism of action Preclinical research trials found that basimglurant has a high specificity for the glutamate receptor mGlu5, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dystonia
Dystonia is a neurology, neurological Hyperkinesia, hyperkinetic Movement disorders, movement disorder in which sustained or repetitive muscle contractions occur involuntarily, resulting in twisting and repetitive movements or abnormal fixed postures. The movements may resemble a tremor. Dystonia is often intensified or exacerbated by physical activity, and symptoms may progress into adjacent muscles. The disorder may be Heredity, hereditary or caused by other factors such as birth trauma (physical), birth-related or other Injury, physical trauma, infection, poisoning (e.g., lead poisoning) or reaction to Medication, pharmaceutical drugs, particularly Antipsychotic, neuroleptics, or stress. Treatment must be highly customized to the needs of the individual and may include oral medications, chemodenervation Botulinum toxin, botulinum neurotoxin injections, physical therapy, or other supportive therapies, and surgical procedures such as deep brain stimulation. Classification The ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Parkinsonian
Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia (slowed movements), rigidity, and postural instability. Both hypokinetic features (bradykinesia and akinesia) and hyperkinetic features (cogwheel rigidity and tremors at rest) are displayed in parkinsonism. These are the four motor signs that are found in Parkinson's disease (PD)after which Parkinsonism is namedand in dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), and many other conditions. This set of signs occurs in a wide range of conditions and may have many causes, including neurodegenerative conditions, drugs, toxins, metabolic diseases, and neurological conditions other than Parkinson's disease. Signs and symptoms Parkinsonism is a clinical syndrome characterized by the four motor signs that are found in Parkinson's disease: tremor, bradykinesia (slowed movements), rigidity, and postural instability. Parkinsonism gait problems can lead to falls and serious physical i ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
