Novel psychoactive substances (NPSs) have currently become a major public health concern because of relatively easy accessibility to these compounds and difficulty in identifying them with routine laboratory techniques. Here, we report the 18F-fluorodeoxyglucose positron emission tomography/computerized tomography (18F-FDG PET/CT) case study of a 23-year-old man who developed a substance-induced psychotic disorder after having intravenously injected himself with an unspecified amount of methoxetamine (MXE), a ketamine derivative hallucinogen. From a clinical perspective, a blunted affective responsiveness with diminished social drive and sense of purpose, along with a profound detachment from the environment, was observed. Psychometric and neuropsychological assessments highlighted severe dissociative symptoms and lack of motivation, along with a mild impairment of verbal fluency, working memory, and attention. Patient\'s 18F-FDG PET/CT scans displayed a significant bilateral deficit of tracer uptake within the dorsolateral prefrontal cortex (DLPFC). DLPFC activity is critical to goal-oriented cognitive functions, including working memory and sustained attention. DLPFC is also involved in both the temporal integration across multiple sensory modes and in the volitional control of actions, leading to the possibility to construct logically coherent temporal configurations of thought, speech, and behavior. This report highlights that a single acute MXE intoxication may produce severe brain impairment.

In the EU, chemicals with a production or import volume in quantities of one metric ton per year or more have to be tested for skin sensitizing properties under the REACH regulation. The murine Local Lymph Node Assay (LLNA) and its modifications are widely used to fulfil the data requirement, as it is currently considered the first-choice method for in vivo testing to cover this endpoint. This manuscript describes a case study highlighting the importance of understanding the chemistry of the test material during testing for \'skin sensitization\' of MCDA (mixture of 2,4- and 2,6-diamino-methylcyclohexane) with particular focus on the vehicle used. While the BrdU-ELISA modification of the LLNA using acetone/olive oil (AOO) as vehicle revealed expectable positive results. However, the concentration control analysis unexpectedly revealed an instability of MCDA in the vehicle AOO. Further studies on the reactivity showed MCDA to rapidly react with AOO under formation of various imine structures, which might have caused the positive LLNA result. The repetition of the LLNA using propylene glycol (PG) as vehicle did not confirm the positive results of the LLNA using AOO. Finally, a classification of MCDA as skin sensitizer according to the Globally Harmonized System (GHS) was not justified.

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.

Methoxetamine (MXE) is a psychoactive substance distributed mostly via the Internet and is not liable to legal regulation in Poland. MXE has a toxicity profile similar to that of ketamine but longer-lasting effects. The paper describes a case of acute poisoning that resulted from recreational use of MXE and amphetamine and ended in death. In mid-July 2012, a 31-year old man was admitted to the clinical toxicology unit in Gdańsk because of poisoning with an unknown psychoactive substance. The patient was transported to the emergency department (ED) at 5:15 a.m. in a very poor general condition, in a deep coma, with acute respiratory failure, hyperthermia (> 39°C) and generalized seizures. Laboratory tests showed marked leukocytosis, signs of massive rhabdomyolysis, hepatic failure and beginning of acute renal failure. Despite intensive therapy, the patient died 4 weeks after the poisoning in the course of multi-organ dysfunction syndrome. Chemical and toxicological studies of serum and urine samples collected on the poisoning day at 1:40 p.m. confirmed that amphetamine and MXE had been taken earlier that day. Concentration of amphetamine in the serum (0.06 μg/ml) was within the non-toxic range, while MXE (0.32 μg/ml) was within the toxic range of concentrations. Amphetamine was also detected in the patient\'s hair, which suggested a possibility of its use within the last dozen weeks or so. The serious clinical course of intoxication and co-existence of amphetamine and MXE in the patient\'s blood and urine suggest the possibility of adverse interactions between them.

Methoxetamine ((RS)2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone)) is becoming a drug of interest among practitioners of forensic toxicology. In this case report, we describe the case background, standard field sobriety tests, sampling, and analysis of this drug in a whole blood sample as well as screening methods and analysis from a driver operating under the influence of intoxicating substances. Methoxetamine was isolated from the blood sample using mixed mode solid phase extraction. After elution and evaporation, the residue was dissolved in mobile phase (consisting of acetonitrile and aqueous formic acid) for analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC-MS). The case sample was found to contain clonazepam, 7-aminoclonazepam, carboxy-THC, Ddphenhydramine, and MDMA. The case sample was found to contain 10 ng/mL of the drug (methoxetamine) in whole blood. The results of this drug analysis and previous analyses are discussed in terms of this driver operating under the influence of drugs.

Methoxetamine (MXE) is a novel synthetic drug, structurally related to phencyclidine, with ketamine-like properties. Available in Poland since 2010, with no legal control, is adverti. sed as the \"ideal dissociation drug\". The aim of this study was to present a case of nasal methoxetamine acute poisoning in a 28-year-old man, the course of treatment, and the method of identification of this substance in serum and urine. In the course of this intoxication extreme agitation and aggression with slight response to benzodiazepines were observed. The patient was confused, hallucinated. In addition, the physical examination re. vealed tachycardia 120/min and normal blood pressure (130/80 mm Hg). The period of acute poisoning was covered by amnesia. The MXE concentrations in serum and urine were determined using liquid chromatography-mass spectrometry (LC-MS-MS) method, and were respectively 270 ng/ml and 660 ng/ml. Confirmed MXE poisoning increases our knowledge about this new substance, providing relevant clinical and analytical data.

Methoxetamine (MXE) is an analogue of ketamine.
METHODS: We present a 25-year-old male who, after getting an information from the Internet, started to use MXE to avoid the excitement connected with recreational codeine abuse. For about 8 - 10 months he injected about 100 mg of MXE intramuscularly. On the day of admission the patient decided to take much higher dose of 750 mg of MXE. For the first 3-4 hours of hospitalization the profound agitation, which demanded the usage of high doses of benzodiazepines, was observed every several minutes. After 6-7 hours of supportive treatment the patient returned to his baseline mental status.
CONCLUSIONS: MXE presents the new healthcare threat because of easy accessibility via Internet, and lack of legal restrictions in many countries. The low dose of MXE can cause \"peace and serenity\", however, higher dose may act opposite.

Methoxydine (4-MeO-PCP) and Methoxetamine (3-MeO-2-Oxo-PCE) are both commercially produced designer drugs with structural and biochemical similarities to phencyclidine (PCP). Although phencyclidine toxicity is well documented, its recreational use in present times is rare. With the advent of new designer drugs being available widely through internet sites, Acute Physicians should be aware of the clinical features and management of these potential toxins. We present a case of methoxydine ingestion (which to our knowledge has not been previously documented in any medical journals) and a case of methoxetamine ingestion, and discuss their history, contrasting clinical features and acute management.

On the basis of the material available both in the scientific literature and on the web, this paper aims to provide a pharmacological, chemical and behavioural overview of the novel compound methoxetamine. This is a dissociative drug related to ketamine, with a much longer duration of action and intensity of effects. A critical discussion of the availability of information on the web of methoxetamine as a new recreational trend is here provided. Those methodological limitations, which are intrinsically associated with the analysis of online, non-peer reviewed, material, are here discussed as well. It is concluded that the online availability of information on novel psychoactive drugs, such as methoxethanine, may constitute a pressing public health challenge. Better international collaboration levels and novel forms of intervention are necessary to tackle this fast-growing phenomenon.

When they were independently tested, the enantiomers of N,N\'-bis(salicylidene)-trans-1,2-cyclohexanediamine showed a large difference in adsorption on new chiral selectors using microbatch technology. Surprisingly, when these enantiomers were applied on the same supports as a racemic mixture, no discrimination was observed even though suitable adsorption existed. When a mixture enriched in one enantiomer (scalemic mixture) was applied, the resulting supernatant contained the racemic form and the enantiomer in excess was adsorbed on the support together with a part of racemate. This behavior, which militates in favor of a strong heterochiral dimer formation in the racemate, was revealed using microbatch technology but remained hidden on classical column chromatography on chiral support. Molecular dynamics calculations corroborate this hypothesis, showing a favorite binding mode of the heterochiral dimer, which is stabilized by various inter- and intramolecular interactions. Our findings may be considered as a new limitation of microbatch technology, but they may have some inference in case of chiral amplification using the N,N\'-bis(salicylidene)-trans-1,2-cyclohexanediamine enantiomers as chiral ligands.