In Vitro and In Vivo Pharmaco-Toxicological Characterization of 1-Cyclohexyl-x-methoxybenzene Derivatives in Mice: Comparison with Tramadol and PCP.
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
International journal of molecular sciences July 17, 2021 DOI: 10.3390/ijms22147659 via PubMed
Summary
AI-generated from the abstractA novel psychoactive substance, 1-cyclohexyl-x-methoxybenzene, exists as three stereoisomers (ortho, meta, para) structurally similar to tramadol and phencyclidine. In vitro tests showed all three stereoisomers and tramadol were inactive at mu, kappa, and delta opioid receptors. In mice, systemic administration of the stereoisomers impaired sensorimotor responses, altered spontaneous motor activity, produced modest analgesia, and affected thermoregulation and cardiorespiratory responses, resembling effects of tramadol and phencyclidine. Naloxone only partially prevented visual sensorimotor impairments from the stereoisomers, not other effects. The findings indicate these derivatives cause pharmaco-toxicological effects through both opioid and non-opioid mechanisms, suggesting potential for abuse and harm.
Study at a glance
| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | meta tramadol phencyclidine naloxone |
| Keywords | 1-cyclohexyl-x-methoxybenzene Pcp Behavior Mice Novel psychoactive substances |
| Key finding | 1-cyclohexyl-x-methoxybenzene stereoisomers impair sensorimotor responses, modulate motor activity, induce modest analgesia, and alter thermoregulation and cardiorespiratory responses in mice, with naloxone only partially preventing visual sensorimotor impairments. |
Abstract
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.