Kang, H and Park, P and Bortolotto, ZA and Brandt, SD and Colestock, T and Wallach, J and Collingridge, GL and Lodge, D (2016) Ephenidine: A new psychoactive agent with ketamine-like NMDA receptor antagonist properties. Neuropharmacology. ISSN 1873-7064
NEUROPHARM-D-16-00665.R1.pdf - Accepted Version
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To avoid legislation based on chemical structure, research chemicals, frequently used for recreational purposes, are continually being synthesized. N-Ethyl-1,2-diphenylethanamine (ephenidine) is a diarylethylamine that has recently become popular with recreational users searching for dissociative hallucinogenic effects. In the present study, the pharmacological basis of its neural actions has been investigated, initially by assessing its profile in central nervous system receptor binding assays and subsequently in targeted electrophysiological studies. Ephenidine was a potent inhibitor of 3H-MK-801 binding (Ki: 66 nM), implying that it acts at the PCP site of the N-methyl-d-aspartate (NMDA) receptor. It also showed modest activity at dopamine (379 nM) and noradrenaline (841 nM) transporters and at sigma 1 (629 nM) and sigma 2 (722 nM) binding sites. In experiments of extracellular recording of field excitatory postsynaptic potentials (fEPSPs) from area CA1 of rat hippocampal slices, ephenidine, 1 and 10 μM, respectively, produced a 25% and a near maximal inhibition of the NMDA receptor mediated fEPSP after 4 h superfusion. By contrast, ephenidine (50 μM) did not affect the AMPA receptor mediated fEPSPs. In whole cell patch clamp recordings, from hippocampal pyramidal cells, ephenidine (10 μM) blocked NMDA receptor-mediated EPSCs in a highly voltage-dependent manner. Additionally, ephenidine, 10 μM, blocked the induction of long term potentiation (LTP) in CA1 induced by theta burst stimulation. The present data show that the new psychoactive substance, ephenidine, is a selective NMDA receptor antagonist with a voltage-dependent profile similar to ketamine. Such properties help explain the dissociative, cognitive and hallucinogenic effects in man.
|Uncontrolled Keywords:||1109 Neurosciences, 1115 Pharmacology And Pharmaceutical Sciences, 1701 Psychology|
|Subjects:||R Medicine > RM Therapeutics. Pharmacology|
|Divisions:||Pharmacy & Biomolecular Sciences|
|Date Deposited:||15 Aug 2016 12:04|
|Last Modified:||15 Aug 2016 12:04|
|DOI or Identification number:||10.1016/j.neuropharm.2016.08.004|
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- Ephenidine: A new psychoactive agent with ketamine-like NMDA receptor antagonist properties. (deposited 15 Aug 2016 12:04) [Currently Displayed]
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