2-Arachidonyl-glyceryl ether

The best studied of the endocarmabinoids are anandamide (A -arachidonyl-ethanolamine, AEA)(1) and 2-arachidonylglycerol (2-AG)(2). Anandamide was first identified from porcine brain extracts by Devane and co-workers in 1992 [13], while 2-AG was first reported in 1995 to have been isolated from canine gut [14] and rat brain [15]. More recently, noladin ether (2-arachidonyl-glyceryl ether, 2-AGE)(3) [16], virodhamine (D-arachidonyl-ethanolamine)(4) [17] and A-arachidonyl-dopamine (NADA)(5) [18] were proposed as endogenous ligands for the cannabinoid receptors. In a subsequent publication, the authors failed to detect noladin ether in mammalian brains and questioned the relevance of this compound as an endocarmabinoid [19]. Anandamide, noladin ether and NADA have functional selectivity for CBi receptors, virodhamine is CB2 selective and 2-AG is essentially non-selective. 

Arachidonyl glyceryl ether (noladin ether), isolated from porcine brain, is an example of a third, ether-type endocannabinoid. The name is derived from the Hebrew word nolad, what means to be born. The... 

Hanus L, Abu-Lafi S, Pride E, Breuer A, Vogel Z, Shalev DE, Kustanovich 1, Mechoulam R, 2-arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid GBl receptor, PNAS 98 3662—3665, 2001. 

Hanus, L., Abu-Lafi, S., Fride, E., Breuer, A., Vogel, Z., Shalev, D. E., Kustanovich, I., and Mechoulam, R. (2001). 2-Arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CBi receptor. Proc. Natl Acad. Sci. USA 98, 3662-3665. 

Hansen HS, Aitmann A (2008) Endocannabrnoids and nutrition. J Neuroendocrinol 20 94—99 Hansson HA, Rozell B, Skottner A (1987) Rapid axoplasmic transport of insulin-like growth factor 1 in the sdatic nerve af adult rats. Cell Tissue Res 247 241—247 I [anus L, Abu-Lafi S, Fride E, Breuer A, Vogel Z, Shalev DE, Kustanovich 1, Mechoulam R (2001) 2-Arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CBl receptor. Pioc Natl Acad Sd U S A 98 3662-3665... 

The subsequent discovery of the endocannabinoids, arachidonoylethanolamine (anandamide) (Devane et al. 1992b Hanus et al. 1993) and 2-arachidonoyl glycerol (2-AG) (Di Marzo 1998 Mechoulam et al. 1995 Stella et al. 1997) has led to a better understanding of the physiological and biochemical roles of the endocannabinoid system. 2-Arachidonyl glyceryl ether, also known as noladin ether (Hanus et al. 2001), has been proposed as a representative of a third endocannabinoid class. However, noladin ether s pathway of formation has not been characterized and its occurrence in the normal brain has been questioned (Oka et al. 2003). 

An ether-type endocannabinoid, 2-arachidonyl glyceryl ether (noladin ether, 54, Fig. 13) was reported to be isolated from porcine brain (Hanus et al. 2001). Noladin ether was found to bind selectively to the CBi receptor (Kj = 21.2 nM) and cause sedation, hypothermia, intestinal immobility, and mild antinociception in... 

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