Ephenidine: A new psychoactive agent with ketamine-like NMDA receptor antagonist properties
Heather Kang, Pojeong Park, Zuner A. Bortolotto, Simon D. Brandt, Tristan Colestock, Jason Wallach, Graham L. Collingridge, David Lodge
Neuropharmacology August 10, 2016 DOI: 10.1016/j.neuropharm.2016.08.004 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rat hippocampal slices |
| Intervention | Ephenidine |
| Dose | 1 μM, 10 μM, 50 μM |
| Duration | 4-hour superfusion |
| Measures | H-MK-801 binding, field excitatory postsynaptic potentials (fEPSPs), whole cell patch clamp recordings, long term potentiation (LTP) |
| Topics | Esketamine Ketamine |
| Keywords | Nmda receptor Long-term potentiation Ampa receptor Excitatory postsynaptic potential Pharmacology Sigma-1 receptor Glutamate receptor Dizocilpine Ifenprodil Hippocampal formation Biophysics Agonist Biochemistry |
| Citations | 29 |
| Key findings | Ephenidine is a selective NMDA receptor antagonist with a voltage-dependent profile similar to ketamine, blocking NMDA receptor-mediated synaptic transmission and long-term potentiation. |
Abstract
H-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. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'.