Synthesis and Pharmacological Profiling of the Metabolites of Synthetic Cannabinoid Drugs APICA, STS-135, ADB-PINACA, and 5F-ADB-PINACA
| Autor: | Michael Kassiou, Mark Connor, Mitchell Longworth, Samuel D. Banister |
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| Rok vydání: | 2017 |
| Předmět: |
Indazoles
Indoles Cannabinoid receptor Physiology Cognitive Neuroscience medicine.medical_treatment Adamantane Pharmacology 01 natural sciences Biochemistry Membrane Potentials Receptor Cannabinoid CB2 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Receptor Cannabinoid CB1 APICA Synthetic cannabinoids medicine Humans Indole test Indazole Molecular Structure Cannabinoids 010401 analytical chemistry Cell Biology General Medicine 0104 chemical sciences chemistry Cannabinoid ADB-PINACA 030217 neurology & neurosurgery Drug metabolism medicine.drug |
| Zdroj: | ACS Chemical Neuroscience. 8:1673-1680 |
| ISSN: | 1948-7193 |
| Popis: | Synthetic cannabinoids (SCs) containing a 1-pentyl-1-H substituted indole or indazole are abused around the world and are associated with an array of serious side effects. These compounds undergo extensive phase 1 metabolism after ingestion with little understanding whether these metabolites are contributing to the cannabimimetic activity of the drugs. This work presents the synthesis and pharmacological characterization of the major metabolites of two high concern SCs; APICA and ADB-PINACA. In a fluorometric assay of membrane potential, all metabolites that did not contain a carboxylic acid functionality retained potent activity at both the CB1 (EC50 = 14–787 nM) and CB2 (EC50 = 5.5–291 nM) receptors regardless of heterocyclic core or 3-carboxamide substituent. Of note were the 5-hydroxypentyl and 4-pentanone metabolites which showed significant increases in CB2 functional selectivity. These results suggest that the metabolites of SCs potentially contribute to the overall pharmacological profile of these... |
| Databáze: | OpenAIRE |
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