The expanding field of cannabimimetic and related lipid mediators

Abstract

The discovery of the endogenous cannabimimetic lipid mediators, anandamide and 2-arachidonoyl glycerol, opened the door to the discovery of other endogenous lipid mediators similar in structure and function. The majority of these compounds do not bind appreciably to known cannabinoid receptors; yet some of them produce cannabimimetic effects while others exert actions through novel mechanisms that remain to be elucidated. This review explores the growing diversity of recently discovered putative lipid mediators and their relationship to the endogenous cannabinoid system. The possibility that there remain many unidentified signalling lipids coupled with the evidence that many of these yield bioactive metabolites due to actions of known enzymes (e.g. cyclooxygenases, lipoxygenases, cytochrome P450s) suggests the existence of a large and complex family of lipid mediators about which only little is known at this time. The elucidation of the biochemistry and pharmacology of these compounds may provide therapeutic targets for a variety of conditions including sleep dysfunction, eating disorders, cardiovascular disease, as well as inflammation and pain.

Figure 1

Chemical structures of bioactive acyl gylcerols. ^†Indicates compounds with activity at either CB1 or CB2 receptors.

Figure 2

Chemical structures of bioactive acyl ethanolamides. ^†Indicates compounds with activity at either CB1 or CB2 receptors. ^‡Indicates compounds with activity at the TRPV1 receptor. ^*Indicates compounds with activity at the PPARα receptor.

Figure 3

Chemical structures of bioactive acyl dopamines. The TRPV1 agonist, capsaicin, is shown at the bottom to demonstrate the structural similarity to these compounds. ^†Indicates compounds with activity at either CB1 or CB2 receptors. ^‡Indicates compounds with activity at the TRPV1 receptor.

Figure 4

Chemical structures of bioactive acyl amides. ^†Indicates compounds with possible activity at the CB1 receptor. None have shown any activity at CB2 or TRPV1 receptors.

Figure 5

Chemical structure of bioactive acyl amino acids. None have shown any activity at CB1, CB2, or TRPV1 receptors.