Neurological, sensorimotor and cardiorespiratory alterations induced by methoxetamine, ketamine and phencyclidine in mice.

Methoxetamine (MXE), a dissociative drug similar to ketamine and phencyclidine, alters neurological and sensorimotor functions in mice in a dose-dependent manner. Acute systemic administration of MXE, ketamine, and phencyclidine (0.01–30 mg/kg i.p.) differentially affected visual, acoustic, and tactile responses, thermal and mechanical pain, motor activity, and acoustic startle reactivity. MXE and ketamine (1 and 30 mg/kg i.p.) and phencyclidine (1 and 10 mg/kg i.p.) also significantly affected cardiorespiratory parameters and systolic and diastolic blood pressure. The findings suggest MXE produces effects comparable to its parent compounds, with specificity depending on dose and parameter examined.

Study at a glance

Abstract

Novel psychoactive substances are intoxicating compounds developed to mimic the effects of well-established drugs of abuse. They are not controlled by the United Nations drug convention and pose serious health concerns worldwide. Among them, the dissociative drug methoxetamine (MXE) is structurally similar to ketamine (KET) and phencyclidine (PCP) and was created to purposely mimic the psychotropic effects of its "parent" compounds. Recent animal studies show that MXE is able to stimulate the mesolimbic dopaminergic transmission and to induce KET-like discriminative and rewarding effects. In light of the renewed interest in KET and PCP analogs, we decided to deepen the investigation of MXE-induced effects by a battery of behavioral tests widely used in studies of "safety-pharmacology" for the preclinical characterization of new molecules. To this purpose, the acute effects of MXE on neurological and sensorimotor functions in mice, including visual, acoustic and tactile responses, thermal and mechanical pain, motor activity and acoustic startle reactivity were evaluated in comparisons with KET and PCP to better appreciate its specificity of action. Cardiorespiratory parameters and blood pressure were also monitored in awake and freely moving animals. Acute systemic administrations of MXE, KET and PCP (0.01-30 mg/kg i.p.) differentially alter neurological and sensorimotor functions in mice depending in a dose-dependent manner specific for each parameter examined. MXE and KET (1 and 30 mg/kg i.p.) and PCP (1 and 10 mg/kg i.p.) also affect significantly cardiorespiratory parameters, systolic and diastolic blood pressure in mice.