Arachidonoyl ethanolamide,

Koutek, B., et al., Inhibitors of Arachidonoyl Ethanolamide Hydrolysis, The Journal of Biological Chemistry, 269 (37) 22937-22940 (1994). 

Tetrahydrocannabinol (THC), the psychoactive marijuana plant- derived cannabinoid, and numerous synthetic derivatives have been shown to bind to a specific brain receptor, cannabinoid receptor 1 (CBl) (Howlett et al. 1990 Matsuda et al. 1990 Herkenham et al. 1990 Mailleux and Vanderhagen 1992). Arachidonoyl ethanolamide (anandamide), homo—linolenyl ethanolamide, and docosatetraenyl ethanolamide are naturally occurring brain constituents that bind to CBl and as a class are called the anandamides (Mechoulam et al. 

The assays (see above) for arachidonoyl ethanolamide hydrolysis (anandamide amidase) employed H-anandamide as the substrate... 

Akhavan, N. and Deutsch, D.G. Inhibitors of arachidonoyl ethanolamide hydrolysis. J Biol Chem 269(37) 22937-22940, 1994. 

Koutek B, Prestwich GD, Howlett AC, Chin SA, Salehani D, Akhavan N, Deutsch DG (1994) Inhibitors of arachidonoyl ethanolamide hydrolysis. J Biol Chem 269 22937-22940 Kozak KR, Marnett LJ (2002) Oxidative metabolism of endocannahinoids. Prostaglandins... 

Fig. 1. Representative structures ofthe different cannabinoid receptor ligand classes the plant cannabinoid, A -tetrahydrocannabinol the endocannabinoid, arachidonoyl ethanolamide (anandamide) the synthetic pyrazole inverse agonist AM281 and the potent aminoalkylindole agonist AM2233. Both AM281 and AM2233 contain an iodine atom that has been labeled with radioiodine for in vitro and in vivo binding experiments...

Wenger T, Jamali KA, Juaneda C, Leonardelli J, Tramu G (1997) Arachidonoyl ethanolamide (anandamide) activates the parvocellular part of hypothalamic paraventricular nucleus. Biochem Biophys Res Commun 237 724-728... 

The mammalian endocannabinoid family inclndes fonr lipid Af-fatty acyl-ethanolamines (NAEs), two Af-acyl-dopamines, a lipid ester, and a lipid ether. The NAEs are Af-arachidonoyl ethanolamine (anan-damide, AEA) (Devane et al., 1992), docosatetraenoyl-ethanolamide and di-homo-y-hnolenoyl-ethanolamide (Hanus et al., 1993), and O-arachidonoyl ethanolamide (virodhamine) (Porter et al., 2002). The Af-acyl-dopamines are Af-arachidonoyl-dopamine (NADA) and Af-oleoyl-dopamine (Hnang et al., 2002). The lipid ester is sn-2 arachidonoyl glycerol (2-AG) (Mechonlam et al., 1995 Sugiura et al., 1995). The lipid ether is sn-2 arachidonoyl glyceryl ether (noladin ether) (Hanus et al., 2001). 

The discovery of anandamide (arachidonoyl ethanolamide, AEA) and of its manifold roles in the central nervous system and in the periphery (reviewed in refs. 1 and 2) prompted several researchers to develop analytical methods to assay and characterize the activity of the enzymes responsible for AEA metabolism in various cells and tissues. Fatty acid amide hydrolase (arachidonoyl ethanolamide amidohydrolase, EC 3.5.1.4 FAAH) has emerged as the key AEA hydrolase, showing a molecular mass of approx 64 kDa and an optimum pH of around 9.0 (3). Recently, FAAH has been crystallized,and its three dimensional structure has been determined at 2.8A resolution (4). This enzyme cleaves the amide bond and releases arachidonic acid and ethanolamine. High-performance liquid chromatography (HPLC) is the most widely used method to determine FAAH activity from different sources. We developed a new method (5) based on reversed-phase (RP)-HPLC and on-line scintillation counting, which combines the need for high resolution, reproducibility, and sensitivity... 

Mechoulam s group assumed that the presence of a specific caimabinoid receptor indicated the existence of endogenous specific caimabinoid ligands that activate these receptors. Taking into consideration that all plant cannabinoids are lipophilic components, they looked for lipophilic components of porcine brain that bind to the cannabinoid receptor. Indeed, in 1992 they identified the first endogenous cannabinoid (Devane et al., 1992), arachidonoyl ethanolamide, which was named anandamide (Figure 1) based on the Sanskrit word ananda, meaning bliss, as well as on its chemical nature, amide. 

Koutek, B, Prestwich, GD, Hewlett, AC, Chin, SA, Salehani, D, Akhavan, N and Deutsch, DG (1994) Inhibitors of arachidonoyl ethanolamide hydrolysis. 7 B/o/ Chem, 269,22937-22940. 

Snider NT, Walker VJ, Hollenberg PF. Oxidation of the endogenous cannabinoid arachidonoyl ethanolamide by the cytochrome P450 monooxygenases physiological and pharmacological implications. Pharmacol Rev. 2010 62(1) 136-154. 

FIGURE 5.10 Chemical structure of anandamide. Three models of anandamide (arachidonoyl ethanolamide, AEA) are shown. In the first one (on the top) the region inherited from arachidonic acid (C20 4(o6) is framed. Note the four-double bonds in the cis (Z) configuration (see Chapter 1 for a description of unsaturated fatty acids). The ethanolamine part is shaded in rose. The two other models show an energy-minimized structure of anandamide in tube and sphere rendition. The arrows indicate the correspondence of chemical groups between the models. 

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