Anandamides, structure-activity

Pate DW (1999) Anandamide structure-activity relationships and mechanisms of action on intraocular pressure in the normotensive rabbit model. Doctoral dissertation. Kuopio University Publications, Kuopio... 

Jarrahian A, Manna S, Edgemond WS, Campbell WB, Hillard CJ (2000) Structure-activity relationships among N-arachidonylethanolamine (anandamide) head group analogues for the anandamide transporter. J Neurochem 74 2597-2606... 

Ross RA, Gibson TM, Brockie HC, Leslie M, Pashmi G, Craib SJ, Di Marzo V, Pertwee RG (2001) Structure-activity relationship for the endogenous cannabinoid, anandamide, and certain of its analogues at vanilloid receptors in transfected cells and vas deferens. Br J Pharmacol 132 631-640... 

Fowler CJ, Tiger G, Stenstrom A (1997a) Ibuprofen inhibits rat brain deamidation of anandamide at pharmacologicaUy relevant concentrations. Mode of inhibition and structure-activity relationship. J Pharmacol Exp Ther 283 729-734... 

Khanolkar AD, Makriyannis A (1999) Structure-activity relationships of anandamide, an endogenous cannabinoid ligand. Life Sci 65 607-616... 

Thomas BF, Adams IB, Mascarella SW, Martin BR, Razdan RK (1996) Structure-activity analysis of anandamide analogs relationship to a cannabinoid pharmacophore. J Med Chem 39 471-479... 

Some examples of anandamide analogues (AM356, chloroanandamide and ACPA) are presented in Figure 5. A detailed discussion of the structure-activity relationships of anandamide analogues is summarized elsewhere (Khanolkar and Makriyannis, 1999). It should be noted that ... 

The development of SAR for endocannabinoid-derived structures has primarily focused on the anandamide skeleton (1) with a large number of publications addressing the requirements for activity and stability of this scaffold. More recently, some SAR has begun to emerge for the other end-ocannabinoids, in particular 2-AG (2). The following discussion will focus on highlighting some of the main features that contribute to affinity and/or stability each endocannabinoid will be treated separately. A number of detailed reviews on this subject have been published [142-146]. 

We named the active constituent anandamide — based on the Sanskrit word ananda meaning delight, bliss, and on its chemical nature. A juxtaposition of the various analytical data led us to conclude that the structure of anandamide is that of arachidonoylethanolamide. This conclusion was confirmed by synthesis. 

Figure 19.1. Chemical structure of main active ingredient of Cannabis sativa, A9-tetrahydrocannabinol (THC) and the naturally occurring ligand for cannabinoid receptors anandamide (arachidonyl ethanolamide).

Highly sensitive targeted lipidomic approaches are rapidly leading to the identification of new analogs of anandamide (Tan et al., 2006). The two major families of lipids that share common chemical structure with anandamide are FAEs and fatty acid amides. Although many of these lipids show no activity at CB receptors, they are known to bind and activate other receptors, such as transient receptor potential vanilloid type-1 (TRPV-1) and the nuclear receptor peroxisome proliferator-activated (PPAR-a). 

Bisogno T (2008) Endogenous cannabinoids structure and metabohsm. J Neuroendociinol 20 1-9 Bisogno T, Melck D, Bobrov MY, Gretskaya NM, Bezuglov VV, De Petrocellis L, Di Marzo V (2000) N-acyl-dopamines novel synthetic CBl cannabinoid-receptor ligands and inhibitors of anandamide inactivation with cannabimemetic activity in vitro and in vivo. Biochem J 351 817-824... 

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