Allyn C. Howlett*, Barbara Berglund and Lawrence S. Melvin Pages 343 - 354 ( 12 )
Research on the cannabinoid natural products and synthetic drugs has been bolstered recently by major breakthroughs in the understanding of the biochemical pathways and the production of significant new tools in the form of novel chemical structures. Cannabinoid receptors are now defined pharmacologically, anatomically, and at the molecular level as belonging to the seven transmembrane spanning G protein coupled receptor superfarnily. Currently recognized receptor subtypes include the CB1 and CBJ(a) splice variants, found predominantly in the brain, and the CB2 subtype, identified in cells of immunologic origin. Three structurally different classes of cannabinoid receptor agonists have been characterized and serve as pharmacological tools most frequently used to explore drug-receptor interactions both in vitro and in vivo9. -THC and HU-210 characterize the classical ABC-tricyclic cannabinoid structures. CP-55,940 is a prototype of the nonclassical AC-bicyclic synthetic cannabinoids, and CP-55,244 is an ACD-bicyclic structure that defines a novel receptor binding region. WIN-55212-2 is a prototype agonist in the aminoalkylindole series of cannabimimetic structures. Arachidonylethanolamide (anandamide) is an eicosanoid natural product that acts as a cannabinoid agonist. With the advent of a high potency, CB1 receptor-selective antagonist, SR141716A, it is possible that novel cannabinoid receptor subtypes will be able to be distinguished pharmacologically.