Neurological, sensorimotor and cardiorespiratory alterations induced by methoxetamine, ketamine and phencyclidine in mice.
Andrea Ossato, Sabrine Bilel, Adolfo Gregori, Anna Talarico, Claudio Trapella, Rosa Maria Gaudio, Fabio De-Giorgio, Franco Tagliaro, Margherita Neri, Liana Fattore, Matteo Marti
Neuropharmacology October 1, 2018 DOI: 10.1016/j.neuropharm.2018.08.017 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Methoxetamine Ketamine Phencyclidine |
| Dose | 0.01-30 mg/kg i.p. |
| Topics | Ketamine Esketamine |
| Keywords | Behavioral alterations Dissociative drugs Methoxetamine Phencyclidine |
| Key points | Methoxetamine, ketamine, and phencyclidine differentially alter neurological and sensorimotor functions and cardiorespiratory parameters in mice in a dose-dependent manner. |
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.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
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- A combined toxicokinetic and metabolic approach to investigate deschloro-N-ethylketamine exposure in a multidrug user. Journal of Pharmaceutical and Biomedical Analysis June 15, 2024
- Pharmaco-toxicological effects of the novel tryptamine hallucinogen 5-MeO-MiPT on motor, sensorimotor, physiological, and cardiorespiratory parameters in mice-from a human poisoning case to the preclinical evidence. Psychopharmacology March 1, 2024
- New insights into methoxetamine mechanisms of action: Focus on serotonergic 5-HT2 receptors in pharmacological and behavioral effects in the rat. Experimental Neurology November 1, 2021
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Cites 37
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- From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs. Drug Testing and Analysis 2014
- Phenomenon of new drugs on the Internet: the case of ketamine derivative methoxetamine Human Psychopharmacology: Clinical and Experimental March 1, 2012
- The ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor. PLoS One June 14, 2016
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