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
| Autor: | Stephen Bright, Richard C. Kevin, Iain S. McGregor, Cristina Gil Lladanosa, Samuel D. Banister, Mireia Ventura Vilamala, Roy Gerona, Michelle Glass, Mark Connor, Axel Adams, Rochelle Boyd, Monica J. Barratt, Christopher Havel, Christa MacDonald |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Indazoles Indoles Cannabinoid receptor medicine.medical_treatment Pharmaceutical Science Pharmacology Scaffold hopping 01 natural sciences Body Temperature Analytical Chemistry Receptor Cannabinoid CB2 Mice Radioligand Assay 03 medical and health sciences 0302 clinical medicine Receptor Cannabinoid CB1 Cell Line Tumor Radioligand medicine Cumyl-PINACA Animals Humans Environmental Chemistry 030216 legal & forensic medicine Receptor Cells Cultured Spectroscopy Cannabinoid Receptor Agonists Membrane potential Cannabinoids Chemistry 010401 analytical chemistry Amides 0104 chemical sciences Cannabinoid |
| Zdroj: | Drug Testing and Analysis. 11:279-291 |
| ISSN: | 1942-7603 |
| DOI: | 10.1002/dta.2491 |
| Popis: | 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 (CB1 and CB2 , respectively) were assessed using tritiated radioligand competition experiments and fluorescence-based plate reader membrane potential assays. Despite CB1 binding affinities differing by over two orders of magnitude (Ki = 2.95-174 nM), all compounds were potent and efficacious CB1 agonists (EC50 = 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 CB1 -dependent mechanism. |
| Databáze: | OpenAIRE |
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