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

Authors/Creators

• Samuel D. Banister
• Axel Adams
• Richard C. Kevin
• Christa Macdonald
• Michelle Glass
• Rochelle Boyd
• Mark Connor
• Iain S. McGregor
• Christopher M. Havel
• Stephen J. Bright, Edith Cowan UniversityFollow
• Mireia Ventura Vilamala
• Cristina Gil Lladanosa
• Monica J. Barratt
• Roy R. Gerona

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.

Keywords

cannabinoid, mass spectrometry, P7AICA, pharmacology, PINACA

Document Type

Journal Article

Date of Publication

1-1-2019

PubMed ID

30151911

Publication Title

Drug Testing and Analysis

Publisher

John Wiley and Sons Ltd

School

School of Medical and Health Sciences

RAS ID

28154

Comments

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. Available here

Copyright

free_to_read