Syntheses, analytical and pharmacological characterizations of the 'legal high' 4-[1-(3-methoxyphenyl)cyclohexyl]morpholine (3-MeO-PCMo) and analogues.
Tristan Colestock, Jason Wallach, Matt Mansi, Nadine Filemban, Hamilton Morris, Simon P Elliott, Folker Westphal, Simon D Brandt, Adeboye Adejare
Drug testing and analysis February 1, 2018 Peer reviewed DOI: 10.1002/dta.2213 via PubMed
Summary
3-MeO-PCMo, a new psychoactive substance and morpholine analogue of PCP, exhibits moderate affinity for the N-methyl-d-aspartate receptor (NMDAR), comparable to ketamine but about 12 times lower than PCP. Six arylcyclohexylmorpholines were synthesized and characterized, with in vitro binding studies showing that 3-MeO-PCMo's affinity for NMDAR supports reports of its dissociative effects in users. The study also successfully differentiated between three positional isomers.
Study at a glance
| Key finding | 3-MeO-PCMo has moderate affinity for NMDAR, comparable to ketamine and approximately 12-fold lower than PCP. |
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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, namely the 2- and 4-MeO-PCMo isomers, 3,4-methylenedioxy-PCMo (3,4-MD-PCMo), 3-Me-PCMo and PCMo. All six arylcyclohexylmorpholines were synthesized and characterized using 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 (+)-[3-3 H]-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.