The ketamine analogue methoxetamine generalizes to ketamine discriminative stimulus in rats.
Cristiano Chiamulera, Federica Armani, Anna Mutti, Liana Fattore
Behavioural Pharmacology April 1, 2016 DOI: 10.1097/fbp.0000000000000221 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal model, drug discrimination study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Methoxetamine MK-801 lysergic acid methamphetamine |
| Dose | 0.0625, 0.125, 0.25, 0.5, or 1.0 mg/kg for MXE; 0.005-0.1 mg/kg for MK-801; 0.025-0.30 mg/kg for lysergic acid; 0.15-0.60 mg/kg for methamphetamine |
| Topics | Esketamine Ketamine |
| Key points | Methoxetamine and MK-801 fully generalized to the ketamine discriminative stimulus in rats, while lysergic acid and methamphetamine only partially substituted. |
Abstract
Methoxetamine (MXE) is a chemical analogue of ketamine. Originally proposed as a ketamine-like fast-acting antidepressant, owing to similar N-methyl-D-aspartate blocker properties, it is now scheduled for reports of hallucinations and psychosis similar to ketamine and lysergic acid. As little is known about the addictive properties of MXE, the aim of this study was to investigate the similarity between discriminative stimuli of MXE and ketamine, as well as to provide data and protocols that could be used in the future for the characterization of novel ketamine-like drugs. The paradigm used was a two-lever operant conditioning paradigm in which rats were trained to discriminate ketamine (7.5 mg/kg/ml, intraperitoneal) from vehicle. Generalization tests were performed with MXE (0.0625, 0.125, 0.25, 0.5, or 1.0). We also tested the N-methyl-D-aspartate channel blocker MK-801 (0.005-0.1), lysergic acid (0.025-0.30), a serotonergic drug that had similar hallucinogenic effects as ketamine and methamphetamine (0.15-0.60) a drug with no generalization with ketamine, injected intraperitoneally presession (mg/kg). MXE and MK-801 fully generalized to ketamine. Lysergic acid and methamphetamine partially substituted for the ketamine stimulus, although the highest lysergic acid dose showed a 77.7% generalization. The present findings suggest that investigation of 'ketamine-like compounds' should explore not only substances with chemical analogy and common molecular mechanisms with ketamine, but also with similar psychopharmacological effects.
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
Cited by 16
- Sex and Gender Differences in the Effects of Novel Psychoactive Substances. Brain Sciences September 3, 2020
- Detailed pharmacological evaluation of methoxetamine (MXE), a novel psychoactive ketamine analogue—Behavioural, pharmacokinetic and metabolic studies in the Wistar rat Brain Research Bulletin May 4, 2016
- 2-Fluorodeschloroketamine has similar abuse potential as ketamine. Addiction Biology May 1, 2022
- Antidepressants enter cells, organelles, and membranes. Neuropsychopharmacology 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
and 11 more in the library
Cites 18
- From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs. Drug Testing and Analysis 2014
- 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
- From “Special K” to “Special M”: The Evolution of the Recreational Use of Ketamine and Methoxetamine CNS Neuroscience & Therapeutics June 1, 2013
- Methoxetamine (MXE) – A Phenomenological Study of Experiences Induced by a “Legal High” from the Internet Journal of Psychoactive Drugs July 1, 2013
- Salvinorin A fails to substitute for the discriminative stimulus effects of LSD or ketamine in Sprague-Dawley rats. Pharmacology, Biochemistry, and Behavior September 1, 2010
and 13 more in the library