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JZL184
JZL184 is an irreversible inhibitor for monoacylglycerol lipase (MAGL), the primary enzyme responsible for degrading the endocannabinoid 2-arachidonoylglycerol (2-AG). It displays high selectivity for MAGL over other brain serine hydrolases, including the anandamide-degrading enzyme fatty acid amide hydrolase (FAAH), thereby making it a useful tool for studying the effects of endogenous 2-AG signaling, ''in vivo''. Administration of JZL184 to mice was reported to cause dramatic elevation of brain 2-AG 2-Arachidonoylglycerol (2-AG) is an endocannabinoid, an endogenous agonist of the CB1 receptor and the primary endogenous ligand for the CB2 receptor. It is an ester formed from the omega-6 fatty acid arachidonic acid and glycerol. It is presen ... leading to several cannabinoid-related behavioral effects. See also * JZL195 References Cannabinoids Benzodioxoles Tertiary alcohols Piperidines Carbamates Nitrobenzenes {{Cannabinoid-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Monoacylglycerol Lipase
Monoacylglycerol lipase (EC 3.1.1.23; systematic name glycerol-ester acylhydrolase, also known as MAG lipase, acylglycerol lipase, MAGL, MGL or MGLL) is an enzyme that, in humans, is encoded by the ''MGLL'' gene. MAGL is a 33-kDa, membrane-associated member of the serine hydrolase superfamily and contains the classical GXSXG consensus sequence common to most serine hydrolases. The catalytic triad has been identified as Ser122, His269, and Asp239. Function Monoacylglycerol lipase catalyzes a reaction that uses water molecules to break the glycerol monoesters of long-chain fatty acids: : hydrolyses glycerol monoesters of long-chain fatty acids It functions together with hormone-sensitive lipase (LIPE) to hydrolyze intracellular triglyceride stores in adipocytes and other cells to fatty acids and glycerol. MGLL may also complement lipoprotein lipase (LPL) in completing hydrolysis of monoglycerides resulting from degradation of lipoprotein triglycerides. Monoacylglycerol lipa ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
JZL195
JZL195 is a potent inhibitor of both fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), the primary enzymes responsible for degrading the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG), respectively. See also * JZL184 * JNJ-42165279 JNJ-42165279 is a drug developed by Janssen Pharmaceutica which acts as a potent and selective inhibitor of the enzyme fatty acid amide hydrolase (FAAH), with an IC50 of 70 nM. It is described as a covalently binding but slowly reversible se ... References Carbamates Piperazines Nitrobenzenes Cannabinoids {{Cannabinoid-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Enzyme Inhibitor
An enzyme inhibitor is a molecule that binds to an enzyme and blocks its activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which substrate molecules are converted into products. An enzyme facilitates a specific chemical reaction by binding the substrate to its active site, a specialized area on the enzyme that accelerates the most difficult step of the reaction. An enzyme inhibitor stops ("inhibits") this process, either by binding to the enzyme's active site (thus preventing the substrate itself from binding) or by binding to another site on the enzyme such that the enzyme's catalysis of the reaction is blocked. Enzyme inhibitors may bind reversibly or irreversibly. Irreversible inhibitors form a chemical bond with the enzyme such that the enzyme is inhibited until the chemical bond is broken. By contrast, reversible inhibitors bind non-covalently and may spontaneously leave the enzyme, allowing the enzyme to resume its function. Reve ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Piperidines
Piperidine is an organic compound with the molecular formula (CH2)5NH. This heterocyclic amine consists of a six-membered ring containing five methylene bridges (–CH2–) and one amine bridge (–NH–). It is a colorless liquid with an odor described as objectionable, and typical of amines. The name comes from the genus name ''Piper'', which is the Latin word for pepper. Although piperidine is a common organic compound, it is best known as a representative structure element within many pharmaceuticals and alkaloids, such as natural-occurring solenopsins. Production Piperidine was first reported in 1850 by the Scottish chemist Thomas Anderson and again, independently, in 1852 by the French chemist Auguste Cahours, who named it. Both of them obtained piperidine by reacting piperine with nitric acid. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst: : C5H5N + 3 H2 → C5H10NH Pyridine can also be reduce ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tertiary Alcohols
In chemistry, an alcohol is a type of organic compound that carries at least one hydroxyl () functional group bound to a saturated carbon atom. The term ''alcohol'' originally referred to the primary alcohol ethanol (ethyl alcohol), which is used as a drug and is the main alcohol present in alcoholic drinks. An important class of alcohols, of which methanol and ethanol are the simplest examples, includes all compounds which conform to the general formula . Simple monoalcohols that are the subject of this article include primary (), secondary () and tertiary () alcohols. The suffix ''-ol'' appears in the IUPAC chemical name of all substances where the hydroxyl group is the functional group with the highest priority. When a higher priority group is present in the compound, the prefix ''hydroxy-'' is used in its IUPAC name. The suffix ''-ol'' in non-IUPAC names (such as paracetamol or cholesterol) also typically indicates that the substance is an alcohol. However, some compound ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cannabinoids
Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (delta-9-THC), the primary intoxicating compound in cannabis. Cannabidiol (CBD) is a major constituent of temperate Cannabis plants and a minor constituent in tropical varieties. At least 113 distinct phytocannabinoids have been isolated from cannabis, although only four (i.e., THCA, CBDA, CBCA and their common precursor CBGA) have been demonstrated to have a biogenetic origin. It was reported in 2020 that phytocannabinoids can be found in other plants such as rhododendron, licorice and liverwort, and earlier in Echinacea. Phytocannabinoids are multi-ring phenolic compounds structurally related to THC, but endocannabinoids are fatty acid derivatives. Nonclassical synthetic cannabinoids (cannabimimetics) include amin ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tetrad Test
The tetrad test is a series of behavioral paradigms in which rodents treated with cannabinoids such as THC show effects. It is widely used for screening drugs that induce cannabinoid receptor-mediated effects in rodents. The four behavioral components of the tetrad are spontaneous activity, catalepsy, hypothermia, and analgesia. Common assays for these behavioral paradigms are as follows: * Spontaneous activity (or hypomotility) is determined by an open field test, in which a mouse is placed in a cage with perpendicular grid lines, usually spaced by approx. 1 inch. An experimenter counts the number of line crossings by the mouse in a given amount of time. * Catalepsy is determined by the bar test. The mouse is placed on a bar oriented parallel to and approximately 1 inch off of the ground. If the mouse remains immobile on the bar for typically more than 20 seconds, it is considered cataleptic. * Hypothermia (reduced body temperature) is determined by using a rectal probe to measu ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Fatty Acid Amide Hydrolase
Fatty acid amide hydrolase or FAAH (, oleamide hydrolase, anandamide amidohydrolase) is a member of the serine hydrolase family of enzymes. It was first shown to break down anandamide in 1993. In humans, it is encoded by the gene ''FAAH''.; Function FAAH is an integral membrane hydrolase with a single ''N''-terminal transmembrane domain. ''In vitro'', FAAH has esterase and amidase activity. ''In vivo'', FAAH is the principal catabolic enzyme for a class of bioactive lipids called the fatty acid amides (FAAs). Members of the FAAs include: * Anandamide (''N''-arachidonoylethanolamine), an endocannabinoid * 2-arachidonoylglycerol (2-AG), an endocannabinoid. * Other ''N''-acylethanolamines, such as ''N''-oleoylethanolamine and ''N''-palmitoylethanolamine * The sleep-inducing lipid oleamide * The ''N''-acyltaurines, which are agonists of the transient receptor potential (TRP) family of calcium channels. ''FAAH'' knockout mice display highly elevated (>15-fold) levels of ''N'' ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
2-AG
2-Arachidonoylglycerol (2-AG) is an endocannabinoid, an endogenous agonist of the CB1 receptor and the primary endogenous ligand for the CB2 receptor. It is an ester formed from the omega-6 fatty acid arachidonic acid and glycerol. It is present at relatively high levels in the central nervous system, with cannabinoid neuromodulatory effects. It has been found in maternal bovine and human milk. The chemical was first described in 1994-1995, although it had been discovered some time before that. The activities of phospholipase C (PLC) and diacylglycerol lipase (DAGL) mediate its formation. 2-AG is synthesized from arachidonic acid-containing diacylglycerol (DAG). Occurrence 2-AG, unlike anandamide (another endocannabinoid), is present at relatively high levels in the central nervous system; it is the most abundant molecular species of monoacylglycerol found in mouse and rat brain (~5-10 nmol/g tissue). Detection of 2-AG in brain tissue is complicated by the relative ease of its i ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Anandamide
Anandamide (ANA), also known as ''N''-arachidonoylethanolamine (AEA), is a fatty acid neurotransmitter. Anandamide was the first endocannabinoid to be discovered: it participates in the body's endocannabinoid system by binding to cannabinoid receptors, the same receptors that the psychoactive compound THC in cannabis acts on. Anandamide is found in nearly all tissues in a wide range of animals. Anandamide has also been found in plants, including small amounts in chocolate. The name 'anandamide' is taken from the Sanskrit word '' ananda'', which means "joy, bliss, delight", plus amide. Anandamide is derived from the non-oxidative metabolism of arachidonic acid, an essential omega-6 fatty acid. It is synthesized from ''N''-arachidonoyl phosphatidylethanolamine by multiple pathways. It is degraded primarily by the fatty acid amide hydrolase (FAAH) enzyme, which converts anandamide into ethanolamine and arachidonic acid. As such, inhibitors of FAAH lead to elevated anandamide leve ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Serine Hydrolase
Serine hydrolases are one of the largest known enzyme classes comprising approximately ~200 enzymes or 1% of the genes in the human proteome. A defining characteristic of these enzymes is the presence of a particular serine at the active site, which is used for the hydrolysis of substrates. The hydrolysis of the ester or peptide bond proceeds in two steps. First, the acyl part of the substrate (the acid part of an ester or the part of a peptide ending in a carboxyl group) is transferred to the serine, making a new ester or amide bond and releasing the other part of the substrate (the alcohol of an ester or the part of the peptide ending in an amino group) is released. Later, in a slower step, the bond between the serine and the acyl group is hydrolyzed by water or hydroxide ion, regenerating free enzyme. Unlike other, non-catalytic, serines, the reactive serine of these hydrolases is typically activated by a proton relay involving a catalytic triad consisting of the serine, an acidi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
