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
June 6, 2016
S. Brandt, P. Kavanagh, F. Westphal et al.
62 citations
Two new psychoactive substances, AL-LAD and LSZ, which are analogs of LSD, were analytically characterized using multiple techniques including NMR, mass spectrometry, and infrared analysis. In male mice, both compounds produced LSD-like behavioral responses in a head-twitch assay, with dose-dependent effects peaking at 200 µg/kg. LSZ was equipotent to LSD (ED50 = 114.2 nmol/kg vs. 132.8 nmol/kg), while AL-LAD was slightly less potent (ED50 = 174.9 nmol/kg). The direct translation of these potency comparisons to humans requires further study. Providing chemical and pharmacological data on emerging substances aids research communities focused on substance use and forensic identification.
Neuropharmacology
August 10, 2016
Heather Kang, Pojeong Park, Zuner A. Bortolotto et al.
29 citations
Ephenidine, a new psychoactive substance, acts as a selective NMDA receptor antagonist by binding to the PCP site (Ki: 66 nM). It also shows modest activity at dopamine and noradrenaline transporters and at sigma 1 and sigma 2 binding sites. In rat hippocampal slices, ephenidine (1 and 10 μM) inhibited NMDA receptor-mediated field excitatory postsynaptic potentials by 25% and near maximally after 4 hours, without affecting AMPA receptor-mediated responses. It blocked NMDA receptor-mediated EPSCs in a voltage-dependent manner and prevented the induction of long-term potentiation. These properties resemble ketamine and help explain its dissociative, cognitive, and hallucinogenic effects in humans.
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.
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.