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 July 17, 2021 Sabrine Bilel, Micaela Tirri, Raffaella Arfè et al.
A 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.