|
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] |
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] |
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] |
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] |
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] |
Hepatotoxicity
Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury (DILI) is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn from the market after approval. The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Certain medicinal agents, when taken in overdoses (e.g. acetaminophen, paracetamol) and sometimes even when introduced within therapeutic ranges (e.g. halothane), may injure the organ. Other chemical agents, such as those used in laboratories and industries, natural chemicals (e.g., alpha-amanitin), and herbal remedies (two prominent examples being kava, though the causal mechanism is unknown, and comfrey, through pyrrolizidine alkaloid content) can also induce hepatotoxicity. Chemicals that cause liver injury are called hepatotoxins. More than 900 drugs have been implicated ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Clinical Trial
Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, pharmaceutical drug, drugs, medical nutrition therapy, 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 institutional review board, 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 experiment, pi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phases Of Clinical Research
The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases start with testing for drug safety in a few human subjects, then expand to many study participants (potentially tens of thousands) to determine if the treatment is effective. Clinical research is conducted on drug candidates, vaccine candidates, new medical devices, and new diagnostic assays. Description Clinical trials testing potential medical products are commonly classified into four phases. The drug development process will normally proceed through all four phases over many years. When expressed specifically, a clinical trial phase is capitalized both in name and Roman numeral, such as "Phase I" clinical trial. If the drug successfully passes through Phases I, II, and III, it will usually be approved by the national regulatory aut ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
