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Overview of Non-CB1/CB2 Cannabinoid Receptors: Chemistry and Modeling

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endoCANNABINOIDS

Part of the book series: The Receptors ((REC,volume 24))

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Abstract

To date, two cannabinoid receptors, CB1R and CB2R, have been isolated by molecular cloning. The CB1R and CB2R cannabinoid receptors are Class A G protein-coupled receptors (GPCRs) that bind constituents of Cannabis sativa, such as the classical cannabinoid agonist (−)-trans-delta-9-tetrahydrocannabinol [(−)-Δ9-THC (1)]. CB1R and CB2R bind four other structural classes of ligands (see Fig. 2.1): nonclassical cannabinoid agonists typified by 2-[5-Hydroxy-2-(3-hydroxy-propyl)-cyclohexyl]-5-(1-methyl-heptyl)-phenol (CP55,940 (2)), endogenous cannabinoids typified by N-arachidonoylethanolamine (anandamide, AEA (3)) and sn-2-arachidonoylglycerol (2-AG, (4)) (Biochem Pharmacol 50(1):83–90, 1995), aminoalkylindole (AAI) agonists typified by (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpho-linylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone (WIN55,212-2 (5)), and biarylpyrazole antagonists typified by N-(piperidiny-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A (6)) and 1-(2,4-Dichloro-phenyl)-5-(4-iodo-phenyl)-4-methyl-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide (AM251 (7)). A large number of physiological processes are controlled by the endogenous cannabinoids (Cannabinoids, Handbook of experimental pharmacology, Springer, Berlin, 2005). Most of these effects have been attributed to action at either the cannabinoid CB1R or CB2R receptors. Yet there are effects that clearly are not CB1R- or CB2R-mediated. Some of these cannabinoid effects may in fact not be receptor mediated at all. However, there is mounting evidence that suggests the involvement of additional GPCRs in cannabinoid effects, as well as the involvement of transient receptor potential (TRP) channels, such as the TRPV1 channel, and peroxisome proliferator-activated receptors. This chapter examines the chemistry of compounds at GPCRs for which a strong link with the other cannabinoid receptors (CB1R and CB2R) has been made.

The structures illustrated here are CB1R/CB2R ligands

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Acknowledgements

This work was supported by a KO5 award (DA021358) to PR from the National Institutes on Drug Abuse.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, Center for Drug Discovery, University of North Carolina Greensboro, Greensboro, NC, USA

    Evangelia Kotsikorou & Patricia Reggio

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  1. Evangelia Kotsikorou
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  2. Patricia Reggio
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Correspondence to Patricia Reggio .

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Editors and Affiliations

  1. , Anatomy and Cell Biology, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, 19140, Pennsylvania, USA

    Mary E. Abood

  2. National Institutes of Health, Division of Basic Neuroscience and Behav, National Institute on Drug Abuse, 6001 Executive Blvd, Bethesda, 20892, Maryland, USA

    Roger G Sorensen

  3. , Pharmacology and Psychiatry and Behavior, University of Washington, Box 357280, Seattle, 98195, Washington, USA

    Nephi Stella

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Kotsikorou, E., Reggio, P. (2013). Overview of Non-CB1/CB2 Cannabinoid Receptors: Chemistry and Modeling. In: Abood, M., Sorensen, R., Stella, N. (eds) endoCANNABINOIDS. The Receptors, vol 24. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4669-9_2

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