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The chemistry and pharmacology of synthetic cannabinoid SDB‐006 and its regioisomeric fluorinated and methoxylated analogs
Author(s) -
Banister Samuel D.,
Olson Alexander,
Winchester Matthew,
Stuart Jordyn,
Edington Amelia R.,
Kevin Richard C.,
Longworth Mitchell,
Herrera Marco,
Connor Mark,
McGregor Iain S.,
Gerona Roy R.,
Kassiou Michael
Publication year - 2018
Publication title -
drug testing and analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 54
eISSN - 1942-7611
pISSN - 1942-7603
DOI - 10.1002/dta.2362
Subject(s) - chemistry , cannabinoid , synthetic cannabinoids , cannabinoid receptor agonists , potency , cannabinoid receptor , agonist , carboxamide , indole test , designer drug , stereochemistry , pharmacology , chromatography , receptor , drug , biochemistry , in vitro , medicine
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‐1 H ‐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 (CB 1 EC 50 = 19 nM). All methoxy‐ and fluorine‐substituted analogs showed reduced potency compared to SDB‐006, although the 2‐fluorinated analog (EC 50 = 166 nM) was comparable to known synthetic cannabinoid RCS‐4 (EC 50 = 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).