Cannabinol Derivatives: Binding to Cannabinoid Receptors and Inhibition of Adenylylcyclase
- 1 September 1997
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 40 (20) , 3228-3233
- https://doi.org/10.1021/jm970126f
Abstract
Several derivatives of cannabinol and the 1,1-dimethylheptyl homolog (DMH) of cannabinol were prepared and assayed for binding to the brain and the peripheral cannabinoid receptors (CB1 and CB2), as well as for activation of CB1- and CB2-mediated inhibition of adenylylcyclase. The DMH derivatives were much more potent than the pentyl (i.e., cannabinol) derivatives. 11-Hydroxycannabinol (4a) was found to bind potently to both CB1 and CB2 (Ki values of 38.0 ± 7.2 and 26.6 ± 5.5 nM, respectively) and to inhibit CB1-mediated adenylylcyclase with an EC50 of 58.1 ± 6.2 nM but to cause only 20% inhibition of CB2-mediated adenylylcyclase at 10 μM. It behaves as a specific, though not potent, CB2 antagonist. 11-Hydroxycannabinol-DMH (4b) is a very potent agonist for both CB1 and CB2 (Ki values of 100 ± 50 and 200 ± 40 pM; EC50 of adenylylcyclase inhibition 56.2 ± 4.2 and 207.5 ± 27.8 pM, respectively).Keywords
This publication has 18 references indexed in Scilit:
- Structure activity relationships of tetrahydrocannabinol analogues on human cannabinoid receptorsBioorganic & Medicinal Chemistry Letters, 1996
- Molecular characterization of a peripheral receptor for cannabinoidsNature, 1993
- Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid ReceptorScience, 1992
- Synthetic nonpsychotropic cannabinoids with potent antiinflammatory, analgesic, and leukocyte antiadhesion activitiesJournal of Medicinal Chemistry, 1992
- Structure of a cannabinoid receptor and functional expression of the cloned cDNANature, 1990
- Δ6-Tetrahydrocannabinol-7-oic acid, a urinary Δ6-THC metabolite: Isolation and synthesisCellular and Molecular Life Sciences, 1973
- Isolation, Structure, and Partial Synthesis of an Active Constituent of HashishJournal of the American Chemical Society, 1964
- Tetrahydrocannabinol Homologs with Doubly Branched Alkyl Groups in the 3-Position. XVIII1Journal of the American Chemical Society, 1948
- Structure of Cannabinol. V. A Second Method of Synthesis of Cannabinol1Journal of the American Chemical Society, 1940
- 264. Cannabis indica. Part V. The synthesis of cannabinolJournal of the Chemical Society, 1940