MXE is reported to have a similar effect to ketamine. It was often believed to possess opioid properties due to its structural similarity to 3-HO-PCP, but this assumption is not supported by data, which shows insignificant affinity for the μ-opioid receptor by the compound. Recreational use of MXE has been associated with hospitalizations from high and/or combined consumption in the US and UK. Acute reversible cerebellar toxicity has been documented in three cases of hospital admission due to MXE overdose, lasting for between one and four days after exposure. MXE was designed in part in an attempt to avoid the urotoxicity associated with ketamine abuse; it was thought the compound's increased potency and reduced dose would limit the accumulation of urotoxic metabolites in the bladder. Like ketamine, MXE has been found to produce bladder inflammation and fibrosis after high dose, chronic administration in mice. Reports of urotoxicity in humans have yet to appear in the medical literature.
Pharmacology
Pharmacodynamics
MXE acts mainly as a selective and high-affinity NMDA receptor antagonist, specifically of the dizocilpine site. It produces ketamine-like effects. In addition to antagonism of the NMDA receptor, MXE has been found to act as a serotonin reuptake inhibitor. Conversely, it shows little or no effect on the reuptake of dopamine and norepinephrine. Nonetheless, MXE has been found to activate dopaminergicneurotransmission, including in the mesolimbic reward pathway. This is a characteristic that it shares with other NMDA receptor antagonists, including ketamine, PCP, and dizocilpine. Animal studies suggest MXE may have rapidly-acting antidepressant effects similar to those of ketamine. A study that assessed binding of MXE at 56 sites including neurotransmitter receptors and transporters found that MXE had Ki values of >10,000 nM for all sites except the dizocilpine site of the NMDA receptor and the serotonin transporter.
MXE is an arylcyclohexylamine and a derivative of eticyclidine. It can also be thought of as the β-Keto-derivative of 3-methoxyeticyclidine, or the N-ethyl homologue of methoxmetamine. It is closely related structurally to ketamine, and more distantly to PCP. MXE hydrochloride is soluble in ethanol up to 10 mg/ml at 25 °C.
Detection in body fluids
A forensic standard of MXE is available, and the compound has been posted on the Forendex website of potential drugs of abuse.
History
The qualitative effects of MXE were first described online in May 2010 and the compound became commercially available on a small scale in September 2010, by November use and sale of the MXE had increased enough for it to be formally identified by the European Monitoring Centre for Drugs and Drug Addiction. By July 2011, the EMCDDA had identified 58 websites selling the compound at a cost of 145–195 euros for 10 grams.
Society and culture
Media coverage
Mixmag reported in January 2012, that people in the dance music and clubbing community have given MXE the slang name 'roflcoptr'. Vice commented that it was likely that the phrase will only be used by "the same politicians, parents and journalists" who called mephedrone 'meow meow'. After being called mexxy in UK Home Officepress releases, the media adopted the name. A literature review was published in March 2012 which looked at scientific literature and information on the web. It concluded that "the online availability of information on novel psychoactive drugs, such as MXE, may constitute a pressing public health challenge. Better international collaboration levels and novel forms of intervention are necessary to tackle this fast-growing phenomenon."
Legal status
United Nations
MXE is one of a few substances which has been controlled under the UN 1971 Convention on Psychotropic Substances since its inception. It was made a schedule 2 drug in November 2016. It is a rare example of a drug being put into schedule II without having an existing medical use.
On 16 June 2014, the European Commission proposed that MXE be banned across the European Union, subjecting those in violation to criminal sanctions. This is following the procedure for risk-assessment and control of new psychoactive substances set up by the council: Decision 2005/387/JHA.
MXE became classified as an illegal narcotic in Israel in May 2012.
United Kingdom
Prior to March 2012, MXE was not controlled by the UK's Misuse of Drugs Act. In March 2012, the Home Office referred MXE to the Advisory Council on the Misuse of Drugs for possible temporary controlling under the powers given in the Police Reform and Social Responsibility Act 2011. The ACMD gave their advice on 23 March, with the chair commenting that "the evidence shows that the use of methoxetamine can cause harm to users and the ACMD advises that it should be subject to a temporary class drug order." In April 2012, MXE was placed under temporary class drug control, which prohibits its import and sale for 12 months.
MXE is not scheduled at the federal level in the United States, but it is possible that it could be considered an analog of PCE, in which case purchase, sales, or possession could be prosecuted under the Federal Analog Act. In September 2015, a bill was introduced into Congress that sought to make MXE a Schedule I substance.
