2-(ethylamino)-2-(3-methoxyphenyl)cyclohexan-1-one

or

[2-(3-methoxyphenyl)-2-(ethylamino)-cyclohexanone]

Physico-chemical properties of Methoxetamine [1]

Molecular Formula C₁₅H₂₁NO₂

CAS number 1239943-76-0

Molecular Weight 247.33

Melting point 389℃

Density 1.076 g/cm³

MXE hydrochloride is soluble in ethanol up to 10 mg/ml at 25°C

Free base of 2-(3-methoxyphenyl)-2-(ethylamino)-cyclohexanone react with HCl according to the scheme (Figure 1):

General information of methoxetamine in Recreational use and pharmacology

Methoxetamine (MXE) is a new recreational drug that belongs to the dissociative class of drugs and has anesthetic properties [2]. It has a similar structure to ketamine and phencyclidine. On the streets, MXE is known by several names, such as “Special M”, “Mexxy”, “MXE”, “Kmax”, “M-ket”, and “legal ketamine” [3]. It can be administered orally, by snorting, rectally or by intramuscular injection. The typical recreational dose ranges from 20 to 100 mg, although doses as high as 500 mg have been reported in cases of intoxication.

The effects of MXE begin after 10 to 20 minutes, with a duration of 2 to 3 hours. Some users have reported delayed effects, which may cause them to ingest another dose, leading to an increased risk of accidental overdose. The positive effects of MXE include euphoria, a sense of calm, and serenity. The neutral effects include distortion or loss of sensory perception, while the negative effects include severe dissociation, depersonalization, loss of consciousness, nausea, and vomiting. MXE has been reported to have synergy with Psilocybin, LSD, DMT, Mescaline, Ketamine, and N2O, but it is dangerous when mixed with alcohol, benzodiazepines, opioids, depressants, BDO, GBL, GHB, MDMA, and amphetamine. A lethal mixture is 100 mg MXE with 400 mg MDAI intravenously [4].

The longer duration of MXE compared to ketamine is thought to be due to the ethyl group on the nitrogen. The mechanism of action for MXE is believed to be similar to that of ketamine, which acts through the N-ethyl-D-aspartate (NMDA) receptor antagonism and inhibition of dopamine reuptake. Ketamine, phencyclidine (PCP), and analogues of these substances primarily act on the NMDA receptor as open channel blockers and are classified as dissociative anesthetics. They also interact with other receptors, such as dopamine D2-receptor agonists, 5-HT2 receptors, m and k opioid receptors, s receptors, and muscarinic cholinergic receptors [4]. Chronic treatment with ketamine has been associated with severe symptomatic urinary tract problems, but it is believed that MXE does not produce these adverse effects, which is used as an advantage when marketing the drug [5].

Synthesys of MXE.

MXE is an arylcyclohexylamine and a derivative of eticyclidine (PCE) (Figure 2) [6].

It can be thought of as the β-Keto-derivative of 3-methoxyeticyclidine (3-MeO-PCE) or the N-ethyl homologue of methoxmetamine (MXM) and methoxpropamine (MXPr). MXE and related arylcyclohexylamines can be synthesized by Grignard Cyclopentyl reacting with 3-methoxybenzonitrile to form 3-methoxyphenylcyclopentylketone (Figure 3).

The alpha-bromoketone is then converted to a Schiff’s base with ethylamine, which is heated to form methoxetamine [7]. The synthesis is detailed in a US patent [8].

Other synthesis of MXE metabolites presented in [6].

Conclusion

Methoxetamine is a new recreational dissociative drugs class. MXE were first described online in May 2010. A cost of 145–195 euros per 10 grams.

Bibliography

1. https://pubchem.ncbi.nlm.nih.gov/compound/52911279
2. EMCDDA Annual Report 2010 (PDF) (Report). European Monitoring Centre for Drugs and Drug Addiction. 2010. https://www.drugsandalcohol.ie/14182/1/EMCDDA_AR2010_EN.pdf
3. Piotr Adamowicz Ph.D., Dariusz Zuba Ph.D. Fatal Intoxication with Methoxetamine. JOURNAL OF FORENSIC SCIENCES, 60, 2014, p. 264-268. doi: 10.1111/1556-4029.12594. https://onlinelibrary.wiley.com/doi/abs/10.1111/1556-4029.12594
4. Anette Kjellgren, Ph.D., Kristoffer Jonsson, M.Sc. Methoxetamine (MXE) – A Phenomenological Study of Experiences Induced by a “Legal High” from the Internet. J Psychoactive Drugs. 2013 Jul; 45(3), pp. 276–286. doi: 10.1080/02791072.2013.803647. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756617/
5. Christopher D. Rosenbaum & Stephanie P. Carreiro, Kavita M. Babu Here Today, Gone Tomorrow…and Back Again? A Review of Herbal Marijuana Alternatives (K2, Spice), Synthetic Cathinones (Bath Salts), Kratom, Salvia divinorum, Methoxetamine, and Piperazines. J. Med. Toxicol., 2012, V. 8, pp. 15–32. DOI 10.1007/s13181-011-0202-2. https://link.springer.com/article/10.1007/s13181-011-0202-2
6. B. Jurasek, M. Himl, R. Jurok etc. Synthesis of methoxetamine, its metabolites and deuterium labelled analog as analytical standards and their HPLC and chiral capillary electrophoresis separation. RSC Advances, 2017, vol. 7, pp. 56691-56696. DOI: 10.1039/C7RA10893A. https://pubs.rsc.org/en/content/articlehtml/2017/ra/c7ra10893a#cit22
7. P. A. Hays, J. F. Casale and A. L. Berrier, Microgram J., 2012, 9, 3–17. https://erowid.org/chemicals/methoxetamine/methoxetamine_chemistry1.pdf
8. Patent US3254124 Calvin L. Stevens AMINOKETONES AND METHODS FOR THEIR PRODUCTION. https://patentimages.storage.googleapis.com/33/5b/1a/345b4df7a74da1/US3254124.pdf