Arachidonylglyceryl ether

There are a series of arachidonic acid derivatives (endogenous cannabinoids) with potent action at cannabinoid receptors. These are anandamide (Af-arachidonylethanolamine) and 2-arachidonylglyceryl ether. The endogenous cannabinoids known as endocannabinoids are present in only small amounts in the brain or other tissues, and appear to be synthesized and released locally on... 

FIGURE 14.1 Four endogenous substances suggested as being endocannabinoids anandamide (N-arachi-donoylethanolamine), 2-AG (2-arachidonoylglycerol), noladin ether (2-arachidonylglyceryl ether), and virodhamine (O-arachidonoylethanolamine). The stracture of the principal cannabinoid of plant origin, A -THC (A -tetrahydrocannabinol), is inserted. 

Figure 1. Structures of A -tetrahydrocannabinol (A -THC) and endocannabinoids. K values of anandamide, 2-arachidonoylglycerol (2-AG) and 2-arachidonylglyceryl ether for CB and CB receptors are presented.

A third type of endocannabinoid is noladin ether (2-arachidonylglyceryl ether) (Figure 1), which was recently isolated from porcine brain (Hanus et al, 2001). In contrast to the chemical nature of anandamide (an amide) and 2-AG (an ester), this endocannabinoid is an ether. Apart from the structural differences, noladin ether also differs from anandamide and 2-AG in its cannabinoid receptor binding. It binds to the CBj cannabinoid receptor (K = 21.2 0.5 nM) and causes sedation, hypothermia, intestinal immobility, and mild antinociception in mice. However, in contrast to anandamide and 2-AG it binds very weakly to the CB receptor (K. > 3000 nM). 

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