Methoxetamine, a novel psychoactive substance with serious adverse pharmacological effects: a review of case reports and preclinical findings
Mary T. Zanda, Paola Fadda, Cristiano Chiamulera, Walter Fratta, Liana Fattore
Behavioural Pharmacology September 1, 2016 DOI: 10.1097/fbp.0000000000000241 (opens in new tab)
Summary
AI-generated from the abstractMethoxetamine (MXE), a novel psychoactive substance sold as a 'legal high,' is chemically similar to ketamine and phencyclidine and acts as a noncompetitive NMDA receptor antagonist. Recent preclinical data show it also stimulates dopamine neurotransmission in the mesolimbic pathway. This review summarizes MXE's behavioral and toxicological effects, its pharmacology, and the frequent adverse effects seen in a growing number of intoxications. The review notes that MXE's potential rapid antidepressant activity, suggested by its similarity to ketamine and supported by recent preclinical findings, requires further investigation.
Study at a glance
| Characteristics | Review Peer reviewed |
|---|---|
| Key finding | Methoxetamine (MXE) has a chemical structure analogous to ketamine and phencyclidine, acts as a noncompetitive NMDA receptor antagonist, and recent preclinical data show it stimulates dopamine neurotransmission in the mesolimbic pathway, which may explain its sought effects and frequent adverse effects. |
Abstract
An increasing number of novel psychoactive substances are currently available and sold as ‘legal highs’ or ‘research chemicals’ accompanied by the indication that they are ‘not for human consumption’. Among those that have emerged in the last few years, methoxetamine (MXE) owes its wide popularity to its easy access on the Internet and its reputation of being a ‘safe’ drug. MXE is an arylcyclohexylamine with a chemical structure analogous to ketamine and phencyclidine, and similar noncompetitive glutamate N-methyl d-aspartate receptor antagonist properties. Yet, very recent preclinical data highlighted a stimulatory effect of MXE on dopamine neurotransmission within the mesolimbic pathway. The aim of this review is to provide an updated review of the behavioral and toxicological effects of MXE as well as the latest findings on its pharmacology that might explain sought effects and frequent occurrence of adverse effects. In light of the growing number of intoxications induced by MXE, knowledge of its short-term and long-term effects is urgently needed. However, the hypothetical rapid antidepressant activity of MXE suggested by its chemical analogy with ketamine and supported by recent preclinical findings deserves further investigation.