Endocannabinoids compounds

Fambert DM, Fowler CJ. (2005) The endocannabinoid system Drug targets, lead compounds, and potential therapeutic applications. / Med Chem 48 5059-5087. 

Our research group expected that additional polyunsaturated fatty acid ethanolamides may be present in the brain. We also identified in porcine brain another two putative endocannabinoids, namely homo-y-linoleoylethanolamide (K = 53.4 5-5 nM) and 7,10,13,16-docosatetraenoylethanolamide (K = 34.4 3.2 nM). The isolation of these two compounds as constituents of porcine brain that bind to the cannabinoid receptor demonstrated that anandamide is not the sole representative of this class of potential mediators. 

The endocannabinoids are accompanied in the brain and other tissues by cannabinoid-like compounds, which however do not bind to the cannabinoid receptors. They are saturated and mono- or diunsaturated congeners, which may affect the metabolism and the function of the endocannabinoids... 

Richardson, 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 360 216-226, 2007. 

Like other arachidonate-derived endogenous compounds the endocannabinoids seem to be synthesized and released by cells on demand. The hydrolysis of phospholipid precursors, also probably embedded in the... 

THE BRAIN S OWN MARIJUANA-LIKE NEUROTRANSMITTER The very high potency and structure of the cannabinoids contained within the marijuana plant enable them to cross the blood—brain barrier and bind to a receptor for the brain s very own endogenous cannabinoid neurotransmitter system. If this were not true, then the marijuana plant would be popular only for its use in making rope, paper, and cloth. The two currently identified neurotransmitters compounds (and there are probably more) in this system are anandamide, from the Sanskrit word amnia () meaning bliss, and 2-AG (2-arachidonoyl-glycerol). Unlike the other neurotransmitters that I ve discussed, these two endocannabinoids are not stored in synaptic vesicles. 

Similar to opioids, the cannabinoid system appears to be intricately involved in normal physiology, specifically in the control of movement, formation of memories, and appetite control. Basic research has discovered that members of this family of compounds have the capacity to protect threatened neurons, thereby slowing neurodegenerative processes that ultimately lead to physical disability. As the function of the physiological role of endocannabinoids becomes clearer, it appears the system may be involved in the pathology of several neurological diseases, specifically multiple sclerosis, spasticity, and pain. In 1999 the German journal, Forschende Komplementar-medizin und Klassische Naturheilkunde (Research in Complementary and Classical Natural Medicine) commented ... 

A fifth pathway, finally, is the well-established secretion of small membrane-permeable mediators by diffusion. This mechanism is used for the secretion of nitric oxide, endocannabinoids, and other important lipidic or gaseous neurotransmitters. The major point of regulation of release here is the synthesis of the respective compounds, not their actual secretion. 

Two subtypes of G protein-coupled receptors for cannabis s psychotropic component, A -tetrahydrocannabinol (THC), have been cloned to date, the cannabinoid CBi and CB2 receptors (Howlett et al. 2004). Yet, five different types of endogenous agonists for these cannabinoid receptors have been identified so far (Fig. 1). These compounds, named endocannabinoids by analogy with THC (Di Marzo and Fontana 1995), are all derived from long-chain polyunsaturated fatty acids. In particular (1) the anandamides are amides of ethanolamine with polyunsaturated fatty acids with at least 20 carbon atoms and three 1,4-diene double bonds. The C20 4 homologue in this series, V-arachidonoylethanolamine (AEA) (Devane et al. 1992), also known simply as anandamide, has been most studied. 

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