Structure–activity relationships of synthetic cannabinoid designer drug RCS-4 and its regioisomers and C4 homologues
Creators
- 1. Department of Radiology, Stanford University School of Medicine, Stanford, USA and School of Chemistry, The University of Sydney, Sydney, Australia
- 2. Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia
- 3. School of Chemistry, The University of Sydney, Sydney, Australia; Global Health Institute, Ecole Polytechnique Fe´de´rale de Lausanne, Lausanne, Switzerland and Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fe´de´rale de Lausanne, Lausanne, Switzerland
- 4. School of Chemistry, The University of Sydney, Sydney, Australia
- 5. School of Psychology, The University of Sydney, Sydney, Australia
- 6. Faculty of Pharmacy, The University of Sydney, Sydney, Australia
- 7. School of Medical Sciences, The University of Auckland, Auckland, New Zealand
- 8. School of Chemistry, The University of Sydney, Sydney, Australia and Faculty of Health Sciences, The University of Sydney, Sydney, Australia
Description
RCS-4 [(4-methoxyphenyl)-1-yl-(1-pentyl-1H-indol-3-yl)methanone] represents the first of several N-alkyl-3-(methoxybenzoyl)indoles identified by forensic scientists as synthetic cannabinoid (SC) designer drugs. Despite the detection of RCS-4 and several analogues (RCS-2, RCS-3, RCS-2-C4, RCS-3-C4, and RCS-4-C4) in products intended for human consumption, relatively little is known about this class of cannabinoids. The synthesis of all regioisomers of RCS-4 and their C4 homologues is described. This study also systematically explored the structure–activity relationships of this class of SCs at human CB1 and CB2 receptors using an in vitro fluorometric imaging plate reader membrane potential assay. All compounds demonstrated agonist activity at CB1 (EC50 = 54–574 nM) and CB2 (EC50 = 4.5–46 nM) receptors, with the C4 homologues showing a preference for CB2 receptors over CB1 receptors (31–42 times). Since most of the analogues (RCS-2, RCS-3, RCS-2-C4, RCS-3-C4 and RCS-4-C4) are not subject to regulation in much of the world, despite their activities towards CB1 and CB2 receptors, there is a possibility that these analogues will emerge on the black market.
Files
Banister_ForensicToxicol_2015-P19-AAM.pdf
Files
(2.2 MB)
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