The chemistry and pharmacology of synthetic cannabinoid SDB-006 and its regioisomeric fluorinated and methoxylated analogs

Samuel D Banister; Alexander Olson; Matthew Winchester; Jordyn Stuart; Amelia R Edington; Richard C Kevin; Mitchell Longworth; Marco Herrera; Mark Connor; Iain S McGregor; Roy R Gerona; Michael Kassiou

doi:10.1002/dta.2362

The chemistry and pharmacology of synthetic cannabinoid SDB-006 and its regioisomeric fluorinated and methoxylated analogs

Drug Test Anal. 2018 Jan 19. doi: 10.1002/dta.2362. Online ahead of print.

Authors

Samuel D Banister¹, Alexander Olson², Matthew Winchester^{2

3}, Jordyn Stuart^{4

5}, Amelia R Edington⁵, Richard C Kevin⁵, Mitchell Longworth⁶, Marco Herrera⁷, Mark Connor⁴, Iain S McGregor⁵, Roy R Gerona², Michael Kassiou⁶

Affiliations

¹ Department of Pathology, Stanford University, Stanford, California, USA.
² Clinical Toxicology and Environmental Biomonitoring Laboratory, University of California San Francisco, San Francisco, California, USA.
³ Department of Biological Sciences, University of Southern California, Los Angeles, California, USA.
⁴ Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.
⁵ School of Psychology, The University of Sydney, Sydney, NSW, Australia.
⁶ School of Chemistry, The University of Sydney, Sydney, NSW, Australia.
⁷ Department of Immunology, Stanford University, Stanford, California, USA.

PMID: 29350472
DOI: 10.1002/dta.2362

Abstract

Synthetic cannabinoids are the largest and most structurally diverse class of new psychoactive substances, with manufacturers often using isomerism to evade detection and circumvent legal restriction. The regioisomeric methoxy- and fluorine-substituted analogs of SDB-006 (N-benzyl-1-pentyl-1H-indole-3-carboxamide) were synthesized and could not be differentiated by gas chromatography-mass spectrometry (GC-MS), but were distinguishable by liquid chromatography-quadrupole time-of-flight-MS (LC-QTOF-MS). In a fluorescence-based plate reader membrane potential assay, SDB-006 acted as a potent agonist at human cannabinoid receptors (CB₁ EC₅₀ = 19 nM). All methoxy- and fluorine-substituted analogs showed reduced potency compared to SDB-006, although the 2-fluorinated analog (EC₅₀ = 166 nM) was comparable to known synthetic cannabinoid RCS-4 (EC₅₀ = 146 nM). Using biotelemetry in rats, SDB-006 and RCS-4 evoked comparable reduction in body temperature (~0.7°C at a dose of 10 mg/kg), suggesting lower potency than the recent synthetic cannabinoid AB-CHMINACA (>2°C, 3 mg/kg).

Keywords: AB-CHMINACA; JWH-018; RCS-4; SDB-006; cannabinoid.