A new dissociative anesthetic, 3-MeO-PCMo, a morpholine analogue of 3-MeO-PCP, was synthesized and characterized along with five related compounds. All six arylcyclohexylmorpholines were analyzed using chromatographic, mass spectrometric, and spectroscopic techniques, allowing differentiation of positional isomers. In vitro binding studies in rat forebrain preparations showed moderate affinity for the N-methyl-D-aspartate receptor (NMDAR), with 3-Me-PCMo having the highest affinity, followed by 3-MeO-PCMo. 3-MeO-PCMo had affinity comparable to ketamine and approximately 12-fold lower than PCP. These findings support anecdotal reports of dissociative effects from 3-MeO-PCMo in humans.
Five deschloroketamine derivatives—deschloro-N-cyclopropyl-ketamine, deschloro-N-ethyl-ketamine, deschloro-N-isopropyl-ketamine, deschloro-N-propyl-ketamine, and deschloroketamine—are primarily metabolized through N-dealkylation, hydroxylation, multiple oxidations, and combinations, plus glucuronidation and N-acetylation. In total, 29 phase I and 10 phase II metabolites were detected in rat urine after a 2 mg/kg body weight dose, using liquid chromatography high-resolution tandem mass spectrometry and gas chromatography-mass spectrometry. For the LC-HRMS/MS standard urine screening approach, compound-specific metabolites were identified and confirmed in pooled human liver microsomes for all derivatives except deschloro-N-cyclopropyl-ketamine. The GC-MS approach detected only non-specific acetylated N-dealkylation metabolites.