2-Arachidonyl glyceryl ether

changed 477197848 2-Arachidonyl glyceryl ether.svg skin-invert-image 220px 2-arachidonoyl glyceryl ether 3D BS.png bg-transparent 220px 2-O-[(5Z,8Z,11Z,14Z)-Icosa-5,8,11,14-tetrae-1-yl]glycerol 2-{[(5Z,8Z,11Z,14Z)-Icosa-5,8,11,14-tetraen-1-yl]oxy}propane-1,3-diol 2-AGE, 2-arachidonylglyceryl ether, Noladin ether, Noladin, HU-310 5545 1/C23H40O3/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-26-23(21-24)22-25/h6-7,9-10,12-13,15-16,23-25H,2-5,8,11,14,17-22H2,1H3/b7-6-,10-9-,13-12-,16-15- CUJUUWXZAQHCNC-DOFZRALJBH correct EBI 146346 correct chemspider 1S/C23H40O3/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-26-23(21-24)22-25/h6-7,9-10,12-13,15-16,23-25H,2-5,8,11,14,17-22H2,1H3/b7-6-,10-9-,13-12-,16-15- correct chemspider CUJUUWXZAQHCNC-DOFZRALJSA-N correct CAS 222723-55-9 correct FDA 0D295FLV8W changed EBI 75913 6483057 OCC(OCCCC\C=C/C/C=C\C\C=C/C\C=C/CCCCC)CO correct chemspider 4983515 C23H40O3 364.56 g/mol 2-Arachidonyl glyceryl ether (2-AGE, Noladin ether, HU-310) is a putative endocannabinoid discovered by Lumír Hanuš and colleagues at the Hebrew University of Jerusalem. It is an ether formed from the alcohol analog of arachidonic acid and glycerol. Its isolation from porcine brain and its structural elucidation and synthesis were described in 2001. Hanus L. Abu-Lafi S. Fride E. Breuer A. Vogel Z. Shalev D. Kustanovich I. Mechoulam R. 2-Arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor 10.1073/pnas.061029898 Proceedings of the National Academy of Sciences 98 7 3662–3665 31108 2001 11259648 2001PNAS...98.3662H free Discovery Lumír Hanuš, Saleh Abu-Lafi, Ester Fride, Aviva Breuer, Zvi Vogel, Deborah E. Shalev, Irina Kustanovich, and Raphael Mechoulam found the endogenous agonist of the cannabinoid receptor type 1 (CB1) in 2000. The discovery was 100 gram of porcine brain, (approximately a single brain) was added to a mixture of 200 mL of chloroform and 200 mL of methanol and mixed in a laboratory blender for 2 minutes. 100 mL of Water was then added, and the mixing process continued for another minute. After this, the mixture was filtered. Two layers then formed and the layer of water-methanol was separated and evaporated when pressure was reduced. Synaptosomal membranes were prepared from 250g of the brains of Sabra male rats. A Hewlett Packard G 1800B GCD system that has a HP-5971 GC with electron ionization detector was used. Production The production of the endocannabinoid is enhanced in normal, but not in endothelium-denuded rat aorta on reacting with carbachol, a parasympathomimetic drug. It potently reduces blood pressure in rats and may represent an endothelium-derived hypotension factor. 2-Arachidonyl glyceryl ether's structure can be determined by mass spectrometry and Rutherford backscattering spectrometry. It was confirmed by comparison with a synthetic sample of the endocannabinoid. It binds to the Cannabinoid receptor type 1 (Ki = 21.2 ± 0.5 nM), which causes sedation, hypothermia, intestinal immobility, and mild antinociception in mice. The endocannabinoid exhibits Ki values of 21.2 nM and >3 μM at the Cannabinoid receptor type 1 and the peripheral cannabinoid receptors."2-Arachidonyl Glycerol ether · Noladin; 2-AG ether (CAS 222723-55-9) || Cayman Chemical". Cayman Chemical. Retrieved 2011-05-29. The presence of 2-AGE in body tissue is disputed. Although a research group from Teikyo University, Kanagawa, Japan could not detect it in the brains of mice, hamsters, guinea-pigs or pigs,Oka S Ether-linked analogue of 2-arachidonoylglycerol (noladin ether) was not detected in the brains of various mammalian species J. Neurochem. 85 6 1374–81 2003 12787057 10.1046/j.1471-4159.2003.01804.x Tsuchie A Tokumura A 3 Muramatsu Mayumi Suhara Yoshitomo Takayama Hiroaki Waku Keizo Sugiura Takayuki 39905742 free two other research groups successfully detected it in animal tissues.Fezza F, Bisogno T, Minassi A, Appendino G, Mechoulam R, Di Marzo V Noladin ether, a putative novel endocannabinoid: inactivation mechanisms and a sensitive method for its quantification in rat tissues FEBS Lett. 513 2–3 294–8 2002 11904167 10.1016/S0014-5793(02)02341-4 2002FEBSL.513..294F 24571810Richardson D, Ortori CA, Chapman V, Kendall DA, Barrett DA Quantitative profiling of endocannabinoids and related compounds in rat brain using liquid chromatography-tandem electrospray ionization mass spectrometry Anal. Biochem. 360 2 216–26 2007 17141174 10.1016/j.ab.2006.10.039 Pharmacology 2-AGE binds with a Ki of 21 nM to the CB1 receptor and 480 nM to the CB2 receptor.Shoemaker JL, Joseph BK, Ruckle MB, Mayeux PR, Prather PL The endocannabinoid noladin ether acts as a full agonist at human CB2 cannabinoid receptors J. Pharmacol. Exp. Ther. 314 2 868–75 2005 15901805 10.1124/jpet.105.085282 10316149 It shows agonistic behaviour on both receptors and is a partial agonist for the TRPV1 channel.Duncan M, Millns P, Smart D, Wright JE, Kendall DA, Ralevic V Noladin ether, a putative endocannabinoid, attenuates sensory neurotransmission in the rat isolated mesenteric arterial bed via a non-CB1/CB2 Gi/o linked receptor Br. J. Pharmacol. 142 3 509–18 2004 15148262 10.1038/sj.bjp.0705789 1574960 After binding to CB2 receptors it inhibits adenylate cyclase and stimulates ERK-MAPK and regulates calcium transients.Shoemaker JL, Ruckle MB, Mayeux PR, Prather PL Agonist-directed trafficking of response by endocannabinoids acting at CB2 receptors J. Pharmacol. Exp. Ther. 315 2 828–38 2005 16081674 10.1124/jpet.105.089474 2759320 In comparison to 2-arachidonoyl glycerol, noladin is metabolically more stable resulting in a longer half-life.Laine K, Järvinen K, Mechoulam R, Breuer A, Järvinen T Comparison of the enzymatic stability and intraocular pressure effects of 2-arachidonylglycerol and noladin ether, a novel putative endocannabinoid Invest. Ophthalmol. Vis. Sci. 43 10 3216–22 2002 12356827 It lowers Intraocular pressure, increases the uptake of GABA in the globus pallidus of ratsVenderova K, Brown TM, Brotchie JM Differential effects of endocannabinoids on [(3)H]-GABA uptake in the rat globus pallidus Exp. Neurol. 194 1 284–7 2005 15899265 10.1016/j.expneurol.2005.02.012 34987539 and is neuroprotective by binding to and activation of PPARα.Sun Y Cannabinoid activation of PPARα; a novel neuroprotective mechanism Br. J. Pharmacol. 152 5 734–43 2007 17906680 10.1038/sj.bjp.0707478 2190030 Alexander SP Garle MJ 3 Gibson C L Hewitt K Murphy S P Kendall D A Bennett A J 29 August 2025 See also 2-Arachidonoylglycerol References Category:CB1 receptor agonists Category:CB2 receptor agonists Category:Lipids Category:Endocannabinoids Category:Arachidonyl compounds Category:Glycerol ethers Category:Diols