{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T19:43:55Z","timestamp":1772826235337,"version":"3.50.1"},"reference-count":83,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2021,7,17]],"date-time":"2021-07-17T00:00:00Z","timestamp":1626480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Anti-Drug Policies Department, Presidency of the Council of Ministers, Italy","award":["\u201cEffects of NPS: development of a multicentre research for the information enhancement of the Early Warning System\u201d to M. Marti"],"award-info":[{"award-number":["\u201cEffects of NPS: development of a multicentre research for the information enhancement of the Early Warning System\u201d to M. Marti"]}]},{"DOI":"10.13039\/501100007109","name":"University of Ferrara","doi-asserted-by":"publisher","award":["FAR 2019 to M. Marti"],"award-info":[{"award-number":["FAR 2019 to M. Marti"]}],"id":[{"id":"10.13039\/501100007109","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007109","name":"University of Ferrara","doi-asserted-by":"publisher","award":["FAR 2020 to M. Marti"],"award-info":[{"award-number":["FAR 2020 to M. Marti"]}],"id":[{"id":"10.13039\/501100007109","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007109","name":"University of Ferrara","doi-asserted-by":"publisher","award":["FAR 2020 to G. Cal\u00f2"],"award-info":[{"award-number":["FAR 2020 to G. Cal\u00f2"]}],"id":[{"id":"10.13039\/501100007109","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["RBFR12LDOW to F. De-Giorgio"],"award-info":[{"award-number":["RBFR12LDOW to F. De-Giorgio"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Catholic University of Rome","award":["Linea D1 grants to F. De-Giorgio"],"award-info":[{"award-number":["Linea D1 grants to F. De-Giorgio"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms22147659","type":"journal-article","created":{"date-parts":[[2021,7,18]],"date-time":"2021-07-18T21:16:48Z","timestamp":1626643008000},"page":"7659","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["In Vitro and In Vivo Pharmaco-Toxicological Characterization of 1-Cyclohexyl-x-methoxybenzene Derivatives in Mice: Comparison with Tramadol and PCP"],"prefix":"10.3390","volume":"22","author":[{"given":"Sabrine","family":"Bilel","sequence":"first","affiliation":[{"name":"Section of Legal Medicine and LTTA Centre, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9337-9184","authenticated-orcid":false,"given":"Micaela","family":"Tirri","sequence":"additional","affiliation":[{"name":"Section of Legal Medicine and LTTA Centre, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2614-2368","authenticated-orcid":false,"given":"Raffaella","family":"Arf\u00e8","sequence":"additional","affiliation":[{"name":"Section of Legal Medicine and LTTA Centre, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Sturaro","sequence":"additional","affiliation":[{"name":"Section of Pharmacology, Department of Neuroscience and Rehabilitation, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0437-5670","authenticated-orcid":false,"given":"Anna","family":"Fantinati","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Pharmaceutical Sciences, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6837-6042","authenticated-orcid":false,"given":"Virginia","family":"Cristofori","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Pharmaceutical Sciences, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5452-5775","authenticated-orcid":false,"given":"Tatiana","family":"Bernardi","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Pharmaceutical Sciences, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Boccuto","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Pharmaceutical Sciences, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Cavallo","sequence":"additional","affiliation":[{"name":"NPS Section and Synthetic Drugs, Central Directorate for Anti-Drug Services (DCSA), 00173 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Cavalli","sequence":"additional","affiliation":[{"name":"NPS Section and Synthetic Drugs, Central Directorate for Anti-Drug Services (DCSA), 00173 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio","family":"De-Giorgio","sequence":"additional","affiliation":[{"name":"Section of Legal Medicine, Department of Health Care Surveillance and Bioethics, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Girolamo","family":"Cal\u00f2","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35122 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Marti","sequence":"additional","affiliation":[{"name":"Section of Legal Medicine and LTTA Centre, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Collaborative Center for the Italian National Early Warning System, Department of Anti-Drug Policies, Presidency of the Council of Ministers, 00186 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,17]]},"reference":[{"key":"ref_1","unstructured":"European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) (2021, March 31). EU Drug Markets Report: In-Depth Analysis. 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