Self Medication with Methoxetamine as an Analgesic Resulting in Significant Toxicity

Maskell, Kevin F.; Bailey, Michael T.; Rose, S. Rutherfoord

doi:10.1093/pm/pnw041

Cited by 6 publications

(3 citation statements)

References 8 publications

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“…Given the recent use of MXE as self‐medication to alleviate chronic foot pain (Maskell et al, ), we evaluated the anti‐nociceptive effects of MXE in two different but complementary tests for analgesia, the tail‐flick and hot‐plate test. The highest dose of MXE tested (5 mg·kg −1 ) increased the latency time of reaction, indicating an analgesic effect, which was brief and did not reach statistical significance in the tail‐flick test but was long‐lasting and significantly different from VEH‐treated group in the hot‐plate test.…”

Section: Discussionmentioning

confidence: 99%

“…In support of its abuse liability, following MXE administration we observed an enhanced level of dopamine in the rat nucleus accumbens shell (NAcS) and a dose‐dependent stimulation of the firing rate and burst firing of dopamine neurons in the ventral tegmental area projecting to the NAcS (Mutti et al, ). Intriguingly, MXE was recently reported to be used for self‐medication purposes to treat chronic foot pain (Maskell et al, ) and post‐traumatic stress disorder (Striebel et al, ), suggesting possible use as an analgesic and calming drug.…”

Section: Introductionmentioning

confidence: 99%

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Methoxetamine affects brain processing involved in emotional response in rats

Zanda

Fadda

Antinori

et al. 2017

British J Pharmacology

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BACKGROUND AND PURPOSEMethoxetamine (MXE) is a novel psychoactive substance that is emerging on the Internet and induces dissociative effects and acute toxicity. Its pharmacological effects have not yet been adequately investigated. EXPERIMENTAL APPROACHWe examined a range of behavioural effects induced by acute administration of MXE (0.5-5 mg·kg À1 ; i.p.) in rats and whether it causes rapid neuroadaptive molecular changes. KEY RESULTS MXE (0.5-5 mg·kgÀ1 ) affected motor activity in a dose-and time-dependent manner, inducing hypermotility and hypomotility at low and high doses respectively. At low and intermediate doses (0.5 and 1 mg·kg À1 ), MXE induced anxious and/or obsessive-compulsive traits (marble burying test), did not significantly increase sociability (social interaction test) or induce spatial anxiety (elevated plus maze test). At a high dose (5 mg·kg À1 ), MXE induced transient analgesia (tail-flick and hot-plate test), decreased social interaction time (social interaction test) and reduced immobility time while increasing swimming activity (forced swim test), suggesting an antidepressant effect. Acute MXE administration did not affect self-grooming behaviour at any dose tested. Immunohistochemical analysis showed that behaviourally active doses of MXE (1 and 5 mg·kg À1 ) increased phosphorylation of ribosomal protein S6 in the medial prefrontal cortex and hippocampus. CONCLUSIONS AND IMPLICATIONSMXE differentially affected motor activity, behaviour and emotional states in rats, depending on the dose tested. As reported for ketamine, phosphorylation of the ribosomal protein S6 was increased in MXE-treated animals, thus providing a 'molecular snapshot' of rapid neuroadaptive molecular changes induced by behaviourally active doses of MXE. Abbreviations

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Methoxetamine affects brain processing involved in emotional response in rats

Zanda

Fadda

Antinori

et al. 2017

British J Pharmacology

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“…The patient apparently, but not admittedly, ingested methoxetamine in December 2011; the drug became available by 2010 in UK and spread to the rest of the world since Chinese laboratories decided to produce it (reported in Maskell et al, 2016). This drug, like other arylcyclohexamines, is a noncompetitive NMDA antagonist that binds the dizocilpine site with higher affinity than ketamine and lower than phencyclidine (PCP) (Roth et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Combined NMDA Inhibitor Use in a Patient With Multisubstance-induced Psychotic Disorder

Caloro

Calabrò²,

Pisa

et al. 2018

Journal of Addiction Medicine

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1,2-Diarylethylamine- and Ketamine-Based New Psychoactive Substances

Wallach

Brandt

2018

Handbook of Experimental Pharmacology

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While phencyclidine (PCP) and ketamine remain the most well-studied and widely known dissociative drugs, a number of other agents have appeared since the late 1950s and early 1960s, when the pharmacological potential of this class was first realized. For example, hundreds of compounds have been pursued as part of legitimate research efforts to explore these agents. Some of these found their way out of the research labs and onto illicit markets of the 1960s and following decades as PCP analogs. Other "illicit analogs" apparently never appeared in the scientific literature prior to their existence on clandestine markets, thus originating as novel innovations in the minds of clandestine chemists and their colleagues. Like so much else in this world, new technologies changed this dynamic. In the 1990s individuals separated by vast geographical distances could now communicate nearly instantaneously with ease through the Internet. Some individuals used this newly found opportunity to discuss the chemistry and psychoactive effects of dissociative drugs as well as to collaborate on the design and development of novel dissociative compounds. Similar to modern pharmaceutical companies and academic researchers, these seekers tinkered with the structure of their leads pursuing goals such as improved duration of action, analgesic effects, and reduced toxicity. Whether all these goals were achieved for any individual compound remains to be seen, but their creations have been let out of the bag and are now materialized as defined compositions of matter. Moreover, these creations now exist not only in and of themselves but live on further as permutations into various novel analogs and derivatives. In some cases these compounds have made their way to academic labs where potential clinical applications have been identified. These compounds reached wider distribution when other individuals picked up on these discussions and began to market them as "research chemicals" or "legal highs". The result is a continuously evolving game that is being played between legislatures, law enforcement, and research chemical market players. Two structurally distinct classes that have appeared as dissociative-based new psychoactive substances (NPS) are the 1,2-diarylethylamines and β-keto-arylcyclohexylamines. Examples of the former include diphenidine and various analogs such as fluorolintane and N-ethyl-lanicemine, and examples of the latter are analogs of ketamine such as methoxetamine, deschloroketamine, and 2-fluoro-2-deschloroketamine. The subject of this chapter is the introduction to some of the dissociative NPS from these classes and their known pharmacology that have emerged on the market in recent years.

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Self Medication with Methoxetamine as an Analgesic Resulting in Significant Toxicity

Cited by 6 publications

References 8 publications

Methoxetamine affects brain processing involved in emotional response in rats

Methoxetamine affects brain processing involved in emotional response in rats

Combined NMDA Inhibitor Use in a Patient With Multisubstance-induced Psychotic Disorder

1,2-Diarylethylamine- and Ketamine-Based New Psychoactive Substances

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