Title

Synthesis and pharmacology of new psychoactive substance 5F-CUMYL-P7AICA, a scaffold- hopping analog of synthetic cannabinoid receptor agonists 5F-CUMYL-PICA and 5F-CUMYL-PINACA

Document Type

Journal Article

PubMed ID

30151911

Publisher

John Wiley and Sons Ltd

School

School of Medical and Health Sciences

RAS ID

28154

Comments

Originally published as: Banister, S. D., Adams, A., Kevin, R. C., Macdonald, C., Glass, M., Boyd, R., . . . Gerona, R. R. (2019). Synthesis and pharmacology of new psychoactive substance 5F-CUMYL-P7AICA, a scaffold- hopping analog of synthetic cannabinoid receptor agonists 5F-CUMYL-PICA and 5F-CUMYL-PINACA. Drug Testing and Analysis, 11(2), 279-291. Original article available here

Abstract

Synthetic cannabinoid receptor agonists (SCRAs) are a dynamic class of new psychoactive substances (NPS), with novel chemotypes emerging each year. Following the putative detection of 5F-CUMYL-P7AICA in Australia in 2016, the scaffold-hopping SCRAs 5F-CUMYL-PICA, 5F-CUMYL-PINACA, and 5F-CUMYL-P7AICA were synthesized and characterized by nuclear magnetic resonance (NMR) spectroscopy, gas chromatography–mass spectrometry (GC–MS), and liquid chromatography–quadrupole time-of-flight–MS (LC–QTOF–MS). Since little is known of the pharmacology of 7-azaindole SCRAs like 5F-CUMYL-P7AICA, the binding affinities and functional activities of all compounds at cannabinoid type 1 and type 2 receptors (CB 1 and CB 2 , respectively) were assessed using tritiated radioligand competition experiments and fluorescence-based plate reader membrane potential assays. Despite CB 1 binding affinities differing by over two orders of magnitude (K i = 2.95–174 nM), all compounds were potent and efficacious CB 1 agonists (EC 50 = 0.43–4.7 nM), with consistent rank order for binding and functional activity (5F-CUMYL-PINACA >5F-CUMYL-PICA >5F-CUMYL-P7AICA). Additionally, 5F-CUMYL-P7AICA was found to exert potent cannabimimetic effects in mice, inducing hypothermia (6°C, 3 mg/kg) through a CB 1 -dependent mechanism. © 2018 John Wiley & Sons, Ltd.

DOI

10.1002/dta.2491

Access Rights

free_to_read

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