PLoS ONE
June 17, 2016
Jason Wallach, Heather Kang, Tristan Colestock et al.
73 citations
1,2-Diarylethylamines such as diphenidine (DPH) and 2-methoxy-diphenidine (2-MXP) are sold as 'legal highs' and have been linked to fatal and non-fatal overdoses. Binding studies at 46 central nervous system receptors show these compounds are relatively selective N-methyl-D-aspartate receptor (NMDAR) antagonists with weak off-target inhibition of dopamine and norepinephrine reuptake. In rats, DPH and 2-MXP significantly reduced prepulse inhibition of startle (PPI), an effect seen with dissociative drugs like phencyclidine (PCP) and ketamine. DPH acted with a median effective dose (ED50) of 9.5 mg/kg, less potent than PCP and ketamine.
Drug Testing and Analysis
April 2, 2013
Jason Wallach, Giorgia de Paoli, Adeboye Adejare et al.
21 citations
Six new psychoactive substances related to PCP and ketamine were synthesized and analyzed: three substituted 1-(1-phenylcyclohexyl)piperidines (3-MeO-, 4-MeO-, and 3-Me-PCP) and three substituted 1-(1-phenylcyclohexyl)pyrrolidine analogues (3-MeO-, 4-MeO-, and 3-Me-PCPy). Mass spectrometry, chromatography, infrared, and NMR spectroscopy characterized all six compounds and their intermediates. Solvent and protonation effects on NMR spectra were examined. Isomeric 3-MeO- and 4-MeO-PCP and PCPy analogues could be distinguished by mass spectrometry. Gas chromatography caused notable degradation of 4-MeO-substituted analytes, especially hydrochloride salts, producing a 1-phenylcyclohex-1-ene nucleus; this degradation was less pronounced with 3-MeO isomers, likely due to para-methoxy group resonance facilitating amine elimination.
Drug testing and analysis
February 1, 2018
Tristan Colestock, Jason Wallach, Matt Mansi et al.
14 citations
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.
Drug Testing and Analysis
September 11, 2015
Jason Wallach, Tristan Colestock, Brian Cicali et al.
13 citations
Fifteen N-alkyl-arylcyclohexylamines, including compounds related to the dissociative substances 3-MeO-PCP, 3-MeO-PCE, and 3-MeO-PCPr, were synthesized and characterized. Analytical methods such as gas chromatography, mass spectrometry, and nuclear magnetic resonance spectroscopy were used. Positional isomers of methoxy-substituted arylcyclohexylamines were readily distinguishable under various analytical conditions. The work provides previously unreported analytical data to aid in identifying newly emerging research chemicals.
Drug Testing and Analysis
April 30, 2019
Michael Dybek, Jason Wallach, Pierce V. Kavanagh et al.
9 citations
Six possible racemic isomers of the research chemical fluorolintane (2-F-DPPy) were synthesized and characterized. The isomers differ by the position of a fluorine substituent on the phenyl or benzyl ring of the 1,2-diarylethylamine structure. Using mass spectrometry, chromatography, nuclear magnetic resonance spectroscopy, and infrared spectroscopy, each isomer was distinguishable. A tandem mass spectrometry method analyzing the [M + H – HF]+ species produced distinct product ions for all six substances, aiding identification of positional isomers that pose challenges for stakeholders confronting new psychoactive substances.
Metabolites
May 8, 2024
Fabian Frankenfeld, Lea Wagmann, Anush Abelian et al.
3 citations
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.
European journal of pharmacology
August 15, 2019
Jason Wallach, Tristan Colestock, Julià Agramunt et al.
Fluorolintane, a 1,2-diarylethylamine sold as a 'research chemical' for dissociative effects, was studied pharmacologically for the first time alongside five related isomers. In vitro binding showed fluorolintane has high affinity for NMDA receptors (Ki = 87.92 nM) and even higher affinities for dopamine transporters (DAT) in most cases. Functional experiments in rat hippocampal slices demonstrated that fluorolintane inhibits NMDA receptor-induced field excitatory postsynaptic potentials and blocks long-term potentiation, consistent with NMDA receptor antagonism. In rats, fluorolintane disrupted prepulse inhibition (a measure of sensorimotor gating) with a median effective dose of 13.3 mg/kg, supporting anecdotal reports of dissociative effects in humans.