CB2 cannabinoid receptor agonist enantiomers HU-433 and HU-308: An inverse relationship between binding affinity and biological potency

Smoum, R. et al. (2015) CB2 cannabinoid receptor agonist enantiomers HU-433 and HU-308: An inverse relationship between binding affinity and biological potency. Proceedings of the National Academy of Sciences of the United States of America, 112(28), pp. 8774-8779. (doi: 10.1073/pnas.1503395112) (PMID:26124120)

Abstract

The significance of the results reported is in two areas. (i) Because the cannabinoid receptor type 2 (CB2) agonists seem to be general protective agents, HU-433, a new specific CB2 agonist, may be of major therapeutic importance. (ii) Enantiomers usually have different activity profiles. We report now that HU-433 and its enantiomer HU-308 are both specific CB2 agonists, but whereas HU-433 is much more potent than HU-308 in the rescue of ovariectomy-induced bone loss and ear inflammation, its binding to the CB2 receptor (through which the activity of both enantiomers takes place) is substantially lower compared with HU-308. This situation questions the usefulness of universal radioligands for comparative binding studies.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Bolognini, Dr Daniele
• Authors: Smoum, R., Baraghithy, S., Chourasia, M., Breuer, A., Mussai, N., Attar-Namdar, M., Kogan, N.M., Raphael, B., Bolognini, D., Cascio, M.G., Marini, P., Pertwee, R.G., Shurki, A., Mechoulam, R., and Bab, I.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Proceedings of the National Academy of Sciences of the United States of America
• Publisher: National Academy of Sciences
• ISSN: 0027-8424
• ISSN (Online): 1091-6490