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ADX88178
ADX88178 is an experimental drug that acts as a positive allosteric modulator for the glutamate receptor mGluR4. It was developed as a potential medication for the treatment of Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ... but had mixed results in animal studies, improving dyskinesia but worsening psychosis-like symptoms. However it has antiinflammatory effects in brain tissue which may make it useful for other indications. References Experimental drugs Pyrimidines Pyrazoles Thiazoles {{nervous-system-drug-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MGluR4
Metabotropic glutamate receptor 4 is a protein that in humans is encoded by the ''GRM4'' gene. Together with GRM6, GRM7 and GRM8 it belongs to Metabotropic glutamate receptor#Group II and Group III, group III of the metabotropic glutamate receptor family. Group III receptors are linked to the inhibition of the cyclic AMP cascade. Activation of GRM4 has potential therapeutic benefits in the treatment of parkinson's disease. Splice variant "taste-GRM4" is involved in the perception of umami taste. Ligands Orthosteric *Cinnabarinic acid, a tryptophan metabolite *LSP1-2111: agonist * LSP4-2022: agonist * LSP2-9166: mixed agonist at mGluR4 and mGluR7 Positive allosteric modulators (PAMs) * ADX88178 * Foliglurax (PXT-002331, DT-1687) * Tricyclic thiazolopyrazole derivative 22a: EC50 = 9 nM, Emax = 120% * ML-128: EC50 = 240 nM, Emax = 182% * Valiglurax (AP-472) (VU0652957) * VU-0418506 * VU-001171: EC50 = 650 nM, Emax = 141%, 36-fold shift * VU0155041: subtype-selective PAM, intrinsi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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] |
Glutamate
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 Essential amino acid, 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 optical rotation, 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 carboxylic acid, carboxyl groups −COOH and one amine, amino group ∠... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Parkinson's Disease
Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become more prevalent as the disease progresses. The motor symptoms are collectively called parkinsonism and include tremors, bradykinesia, spasticity, rigidity as well as postural instability (i.e., difficulty maintaining balance). Non-motor symptoms develop later in the disease and include behavior change (individual), behavioral changes or mental disorder, neuropsychiatric problems such as sleep abnormalities, psychosis, anosmia, and mood swings. Most Parkinson's disease cases are idiopathic disease, idiopathic, though contributing factors have been identified. Pathophysiology involves progressive nerve cell death, degeneration of nerve cells in the substantia nigra, a midbrain region that provides dopamine to the basal ganglia, a system invo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Experimental Drugs
An experiment is a procedure carried out to support or refute a hypothesis, or determine the efficacy or likelihood of something previously untried. Experiments provide insight into cause-and-effect by demonstrating what outcome occurs when a particular factor is manipulated. Experiments vary greatly in goal and scale but always rely on repeatable procedure and logical analysis of the results. There also exist natural experimental studies. A child may carry out basic experiments to understand how things fall to the ground, while teams of scientists may take years of systematic investigation to advance their understanding of a phenomenon. Experiments and other types of hands-on activities are very important to student learning in the science classroom. Experiments can raise test scores and help a student become more engaged and interested in the material they are learning, especially when used over time. Experiments can vary from personal and informal natural comparisons ( ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pyrimidines
Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The other diazines are pyrazine (nitrogen atoms at the 1 and 4 positions) and pyridazine (nitrogen atoms at the 1 and 2 positions). In nucleic acids, three types of nucleobases are pyrimidine derivatives: cytosine (C), thymine (T), and uracil (U). Occurrence and history The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives, including the nucleotides cytosine, thymine and uracil, thiamine (vitamin B1) and alloxan. It is also found in many synthetic compounds such as barbiturates and the HIV drug zidovudine. Although pyrimidine derivatives such as alloxan were known in the early 19th century, a laboratory synthesis of a pyrimidine was not carried out until 1879, when Grimaux reported the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pyrazoles
Pyrazole is an organic compound with the formula . It is a heterocycle characterized as an azole with a 5-membered ring of three carbon atoms and two adjacent nitrogen atoms, which are in ortho-substitution. Pyrazoles are also a class of compounds that have the ring C3N2 with adjacent nitrogen atoms. Pyrazole itself has few applications but many substituted pyrazoles are of commercial interest. Notable drugs containing a pyrazole ring are celecoxib (celebrex) and the anabolic steroid stanozolol. Properties Pyrazole is a weak base, with p''K''b 11.5 (p''K''a of the conjugate acid 2.49 at 25 °C). According to X-ray crystallography, the compound is planar. The two C-N distances are similar, both near 1.33 Å History The term pyrazole was given to this class of compounds by German Chemist Ludwig Knorr in 1883. In a classical method developed by German chemist Hans von Pechmann in 1898, pyrazole was synthesized from acetylene and diazomethane. Preparation Pyrazoles are syn ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
