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Syntheses, analytical and pharmacological characterizations of the “legal high” 4-[1-(3-methoxyphenyl)cyclohexyl]morpholine (3-MeO-PCMo) and analogues

Colestock, C and Wallach, J and Mansi, M and Filemban, N and Morris, H and Elliott, SP and Westphal, F and Brandt, SD and Adejare, A (2017) Syntheses, analytical and pharmacological characterizations of the “legal high” 4-[1-(3-methoxyphenyl)cyclohexyl]morpholine (3-MeO-PCMo) and analogues. Drug Testing and Analysis. ISSN 1942-7611

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Abstract

New psychoactive substances (NPS) are commonly referred to as “research chemicals”, “designer drugs” or “legal highs.” One NPS class is represented by dissociative anesthetics, which include analogues of the arylcyclohexylamine phencyclidine (PCP), ketamine, and diphenidine. A recent addition to the NPS market was 4-[1-(3-methoxyphenyl)cyclohexyl]morpholine (3-MeO-PCMo), a morpholine analogue of 3-MeO-PCP. Although suspected to have dissociative effects in users, information about its pharmacological profile is not available. From clinical and forensic perspectives, detailed analytical data are needed for identification, especially when facing the presence of positional isomers, as these are frequently unavailable commercially. This study presents the analytical and pharmacological characterization of 3-MeO-PCMo along with five additional analogues including the 2- and 4-MeO- isomers, 3,4-methylenedioxy-PCMo (3,4-MD-PCMo), 3-Me-PCMo and PCMo. All six arylcyclohexylmorpholines were synthesized and characterized by chromatographic, mass spectrometric and spectroscopic techniques. The three positional isomers could be differentiated and the identity of 3-MeO-PCMo obtained from an internet vendor was verified. All six compounds were also evaluated for affinity at 46 central nervous system receptors including the N-methyl-D-aspartate receptor (NMDAR), an important target for dissociative anesthetics such as PCP and ketamine. In vitro binding studies using [3H]-MK-801 in rat forebrain preparations revealed moderate affinity for NMDAR in the rank order of 3-Me > 3-MeO >PCMo > 3,4-MD > 2-MeO > 4-MeO-PCMo. 3-MeO-PCMo was found to have moderate affinity for NMDAR comparable to that of ketamine, and had an approximate 12-fold lower affinity than PCP. These results support the anecdotal reports of dissociative effects from 3-MeO-PCMo in humans.

Item Type: Article
Additional Information: This is the accepted version of the following article: Colestock T, Wallach J, Mansi M, et al. Syntheses, analytical and pharmacological characterizations of the “legal high” 4-[1-(3-methoxyphenyl)cyclohexyl]morpholine (3-MeO-PCMo) and analogues. Drug Test Anal. 2017. https://doi.org/10.1002/dta.2213, which has been published in final form at http://dx.doi.org/10.1002/dta.2213
Uncontrolled Keywords: 0301 Analytical Chemistry, 1115 Pharmacology And Pharmaceutical Sciences
Subjects: Q Science > QD Chemistry
R Medicine > RA Public aspects of medicine > RA1001 Forensic Medicine. Medical jurisprudence. Legal medicine
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Wiley
Date Deposited: 09 May 2017 11:00
Last Modified: 12 Jul 2017 11:14
DOI or Identification number: 10.1002/dta.2213
URI: http://researchonline.ljmu.ac.uk/id/eprint/6391

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