Synthetic
Cannabis sativa
CP55,940
HU-210
HU-211
Ab-cannabidiol Ajulemic acid
Endocannabinoids
Arachidonic Acid Metabolites
PhysioIogic
N-arachidonyl ethanolamide
2-arachidonoyl-glycerol 2-arachidonylglycerylether O-arachidonyl ethanolamine
Figure 1. Cannabinoid-based drugs are either derived from the Cannabis plant or produced in the body from arachidonic acid. Many but not all have affinity for cannabinoid receptors. See text for explanation.
suggested the existence of an endogenous ligand with similar activity and the isolation of the first of these was reported in 1992 (Devane et al. 1992). This so-called endocannabinoid was demonstrated to be the arachidonic acid derivative, ^-arachidonoyl ethanolamide (AEA), and since its discovery, several other similar compounds have been isolated and extensively studied including 2-arachidonoyl-glycerol (2-AG) (Mechoulam et al. 1995), 2-arachidonylglycerylether (noladin ether) (Hanus et al. 2001), and O-arachidonoyl ethanolamine (virohdamine) (Porter et al. 2002). Most of the cannabinoid-based drugs and endogenous ligands have immuno-modulating activity and most, but not all, bind to one or both of the two known can-nabinoid receptors, (see below). However, some, such as cannabidiol and HU211, have relatively low affinity for cannabinoid receptors, suggesting that other receptors or molecular mechanisms are involved in the action of these agents. A final class of cannabinoid-based drugs is the receptor antagonists/inverse agonist class. These are structurally quite different from cannabinoids and endocannabinoids and have played an important role in understanding the biology of the endocannabinoid system. A few examples of these are SR141716A (Rimonabant®), AM251, and SR144528 (Fowler et al. 2005).
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