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
© 2018 John Wiley & Sons, Ltd. 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,...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal Article |
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John Wiley & Sons, Ltd.
2018
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| Online Access: | http://hdl.handle.net/20.500.11937/71444 |
| _version_ | 1848762481137156096 |
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| author | Banister, S. Adams, A. Kevin, R. Macdonald, C. Glass, M. Boyd, R. Connor, M. McGregor, I. Havel, C. Bright, S. Vilamala, M. Lladanosa, C. Barratt, Monica Gerona, R. |
| author_facet | Banister, S. Adams, A. Kevin, R. Macdonald, C. Glass, M. Boyd, R. Connor, M. McGregor, I. Havel, C. Bright, S. Vilamala, M. Lladanosa, C. Barratt, Monica Gerona, R. |
| author_sort | Banister, S. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © 2018 John Wiley & Sons, Ltd. 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. |
| first_indexed | 2025-11-14T10:48:15Z |
| format | Journal Article |
| id | curtin-20.500.11937-71444 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:48:15Z |
| publishDate | 2018 |
| publisher | John Wiley & Sons, Ltd. |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-714442018-12-13T09:35:02Z 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 Banister, S. Adams, A. Kevin, R. Macdonald, C. Glass, M. Boyd, R. Connor, M. McGregor, I. Havel, C. Bright, S. Vilamala, M. Lladanosa, C. Barratt, Monica Gerona, R. © 2018 John Wiley & Sons, Ltd. 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. 2018 Journal Article http://hdl.handle.net/20.500.11937/71444 10.1002/dta.2491 John Wiley & Sons, Ltd. restricted |
| spellingShingle | Banister, S. Adams, A. Kevin, R. Macdonald, C. Glass, M. Boyd, R. Connor, M. McGregor, I. Havel, C. Bright, S. Vilamala, M. Lladanosa, C. Barratt, Monica Gerona, R. 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 |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | http://hdl.handle.net/20.500.11937/71444 |