British Journal of Pharmacology
June 1, 1983
Nabil A. Anis, Stephen C. Berry, N.r. Burton et al.
1,415 citations
Ketamine and phencyclidine selectively block excitation of spinal neurons by N-methyl-aspartate (NMA) while leaving responses to quisqualate and kainate largely unaffected. In cats and rats, ketamine reduced responses to L-aspartate more than those to L-glutamate. On Renshaw cells, both drugs reduced acetylcholine responses less than NMA responses but more than quisqualate or kainate responses. Intravenous ketamine (2.5-20 mg/kg) and phencyclidine (0.2-0.5 mg/kg) also selectively blocked NMA-induced excitation. The findings suggest that reducing synaptic excitation mediated via NMA receptors contributes to the anaesthetic and analgesic properties of these dissociative anaesthetics.
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.
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
July 15, 2014
Jason Wallach, Pierce V. Kavanagh, Gavin McLaughlin et al.
26 citations
Diphenidine, a dissociative agent sold as a 'research chemical,' and its isomer 2,2-DEP can be distinguished using gas chromatography-mass spectrometry by their unique iminium ions. The study synthesized and characterized both compounds and their pyrrolidine analogues. Two vendor samples confirmed diphenidine. In rat hippocampal slices, diphenidine (30 μM) reduced NMDA-mediated electrical signals to a similar extent as ketamine (30 μM), indicating it acts on the same receptor. This suggests 1,2-diphenylethylamines are emerging alternatives to arylcyclohexylamine-type dissociatives like PCP and methoxetamine.
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.