In Vitro and In Vivo Pharmaco-Toxicological Characterization of 1-Cyclohexyl-x-methoxybenzene Derivatives in Mice: Comparison with Tramadol and PCP
1-cyclohexyl-x-methoxybenzene is a novel psychoactive substance (NPS), first discovered in Europe in 2012 as unknown racemic mixture of its three stereoisomers: ortho, meta and para. Each of these has structural similarities with the analgesic tramadol and the dissociative anesthetic phencyclidine....
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MDPI AG
2021-07-01
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| Series: | International Journal of Molecular Sciences |
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| author | Sabrine Bilel Micaela Tirri Raffaella Arfè Chiara Sturaro Anna Fantinati Virginia Cristofori Tatiana Bernardi Federica Boccuto Marco Cavallo Alessandro Cavalli Fabio De-Giorgio Girolamo Calò Matteo Marti |
| author_facet | Sabrine Bilel Micaela Tirri Raffaella Arfè Chiara Sturaro Anna Fantinati Virginia Cristofori Tatiana Bernardi Federica Boccuto Marco Cavallo Alessandro Cavalli Fabio De-Giorgio Girolamo Calò Matteo Marti |
| author_sort | Sabrine Bilel |
| collection | DOAJ |
| description | 1-cyclohexyl-x-methoxybenzene is a novel psychoactive substance (NPS), first discovered in Europe in 2012 as unknown racemic mixture of its three stereoisomers: ortho, meta and para. Each of these has structural similarities with the analgesic tramadol and the dissociative anesthetic phencyclidine. In light of these structural analogies, and based on the fact that both tramadol and phencyclidine are substances that cause toxic effects in humans, the aim of this study was to investigate the in vitro and in vivo pharmacodynamic profile of these molecules, and to compare them with those caused by tramadol and phencyclidine. In vitro studies demonstrated that tramadol, ortho, meta and para were inactive at mu, kappa and delta opioid receptors. Systemic administration of the three stereoisomers impairs sensorimotor responses, modulates spontaneous motor activity, induces modest analgesia, and alters thermoregulation and cardiorespiratory responses in the mouse in some cases, with a similar profile to that of tramadol and phencyclidine. Naloxone partially prevents only the visual sensorimotor impairments caused by three stereoisomers, without preventing other effects. The present data show that 1-cyclohexyl-x-methoxybenzene derivatives cause pharmaco-toxicological effects by activating both opioid and non-opioid mechanisms and suggest that their use could potentially lead to abuse and bodily harm. |
| first_indexed | 2024-03-10T09:36:27Z |
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| id | doaj.art-9789d31ef7e94df4b761bc3bde2dcd1b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:36:27Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9789d31ef7e94df4b761bc3bde2dcd1b2023-11-22T04:02:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012214765910.3390/ijms22147659In Vitro and In Vivo Pharmaco-Toxicological Characterization of 1-Cyclohexyl-x-methoxybenzene Derivatives in Mice: Comparison with Tramadol and PCPSabrine Bilel0Micaela Tirri1Raffaella Arfè2Chiara Sturaro3Anna Fantinati4Virginia Cristofori5Tatiana Bernardi6Federica Boccuto7Marco Cavallo8Alessandro Cavalli9Fabio De-Giorgio10Girolamo Calò11Matteo Marti12Section of Legal Medicine and LTTA Centre, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, ItalySection of Legal Medicine and LTTA Centre, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, ItalySection of Legal Medicine and LTTA Centre, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, ItalySection of Pharmacology, Department of Neuroscience and Rehabilitation, University of Ferrara, 44121 Ferrara, ItalyDepartment of Chemistry and Pharmaceutical Sciences, University of Ferrara, 44121 Ferrara, ItalyDepartment of Chemistry and Pharmaceutical Sciences, University of Ferrara, 44121 Ferrara, ItalyDepartment of Chemistry and Pharmaceutical Sciences, University of Ferrara, 44121 Ferrara, ItalyDepartment of Chemistry and Pharmaceutical Sciences, University of Ferrara, 44121 Ferrara, ItalyNPS Section and Synthetic Drugs, Central Directorate for Anti-Drug Services (DCSA), 00173 Rome, ItalyNPS Section and Synthetic Drugs, Central Directorate for Anti-Drug Services (DCSA), 00173 Rome, ItalySection of Legal Medicine, Department of Health Care Surveillance and Bioethics, Università Cattolica del Sacro Cuore, 00168 Rome, ItalyDepartment of Pharmaceutical and Pharmacological Sciences, University of Padua, 35122 Padua, ItalySection of Legal Medicine and LTTA Centre, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy1-cyclohexyl-x-methoxybenzene is a novel psychoactive substance (NPS), first discovered in Europe in 2012 as unknown racemic mixture of its three stereoisomers: ortho, meta and para. Each of these has structural similarities with the analgesic tramadol and the dissociative anesthetic phencyclidine. In light of these structural analogies, and based on the fact that both tramadol and phencyclidine are substances that cause toxic effects in humans, the aim of this study was to investigate the in vitro and in vivo pharmacodynamic profile of these molecules, and to compare them with those caused by tramadol and phencyclidine. In vitro studies demonstrated that tramadol, ortho, meta and para were inactive at mu, kappa and delta opioid receptors. Systemic administration of the three stereoisomers impairs sensorimotor responses, modulates spontaneous motor activity, induces modest analgesia, and alters thermoregulation and cardiorespiratory responses in the mouse in some cases, with a similar profile to that of tramadol and phencyclidine. Naloxone partially prevents only the visual sensorimotor impairments caused by three stereoisomers, without preventing other effects. The present data show that 1-cyclohexyl-x-methoxybenzene derivatives cause pharmaco-toxicological effects by activating both opioid and non-opioid mechanisms and suggest that their use could potentially lead to abuse and bodily harm.https://www.mdpi.com/1422-0067/22/14/76591-cyclohexyl-x-methoxybenzeneopioid receptorstramadolPCPbehaviormice |
| spellingShingle | Sabrine Bilel Micaela Tirri Raffaella Arfè Chiara Sturaro Anna Fantinati Virginia Cristofori Tatiana Bernardi Federica Boccuto Marco Cavallo Alessandro Cavalli Fabio De-Giorgio Girolamo Calò Matteo Marti In Vitro and In Vivo Pharmaco-Toxicological Characterization of 1-Cyclohexyl-x-methoxybenzene Derivatives in Mice: Comparison with Tramadol and PCP International Journal of Molecular Sciences 1-cyclohexyl-x-methoxybenzene opioid receptors tramadol PCP behavior mice |
| title | In Vitro and In Vivo Pharmaco-Toxicological Characterization of 1-Cyclohexyl-x-methoxybenzene Derivatives in Mice: Comparison with Tramadol and PCP |
| title_full | In Vitro and In Vivo Pharmaco-Toxicological Characterization of 1-Cyclohexyl-x-methoxybenzene Derivatives in Mice: Comparison with Tramadol and PCP |
| title_fullStr | In Vitro and In Vivo Pharmaco-Toxicological Characterization of 1-Cyclohexyl-x-methoxybenzene Derivatives in Mice: Comparison with Tramadol and PCP |
| title_full_unstemmed | In Vitro and In Vivo Pharmaco-Toxicological Characterization of 1-Cyclohexyl-x-methoxybenzene Derivatives in Mice: Comparison with Tramadol and PCP |
| title_short | In Vitro and In Vivo Pharmaco-Toxicological Characterization of 1-Cyclohexyl-x-methoxybenzene Derivatives in Mice: Comparison with Tramadol and PCP |
| title_sort | in vitro and in vivo pharmaco toxicological characterization of 1 cyclohexyl x methoxybenzene derivatives in mice comparison with tramadol and pcp |
| topic | 1-cyclohexyl-x-methoxybenzene opioid receptors tramadol PCP behavior mice |
| url | https://www.mdpi.com/1422-0067/22/14/7659 |
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