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'.
Comparable studies
Other experimental studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine activates psychosis and alters limbic blood flow in schizophrenia Schizophrenic individuals | 1995 | Experimental study | |
| The spectral exponent of the resting EEG indexes the presence of consciousness during unresponsiveness induced by propofol, xenon, and ketamine Healthy participants | 2019 | Controlled experimental study | n = 15 |
| Ketamine Increases Human Motor Cortex Excitability to Transcranial Magnetic Stimulation Normal human subjects | 2003 | Experimental study | n = 7 |
| Evidence that Subanesthetic Doses of Ketamine Cause Sustained Disruptions of NMDA and AMPA-Mediated Frontoparietal Connectivity in Humans Human participants | 2015 | Experimental study | |
| Simultaneous population pharmacokinetic modelling of ketamine and three major metabolites in patients with treatment‐resistant bipolar depression Patients with treatment-resistant bipolar depression | 2012 | Population pharmacokinetic analysis | n = 9 |
Citations in the library
Cited by 18
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Effect fingerprinting of new psychoactive substances (NPS): What can we learn from in vitro data? Pharmacology & Therapeutics February 1, 2018
- Ketamine: Neuroprotective or Neurotoxic? Frontiers in Neuroscience September 10, 2021
- Stimulant and hallucinogenic novel psychoactive substances; an update Expert Review of Clinical Pharmacology November 2, 2023
- The novel antidepressant ketamine enhances dentate gyrus proliferation with no effects on synaptic plasticity or hippocampal function in depressive‐like rats Acta Physiologica October 22, 2018
and 13 more in the library
Cites 12
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate British Journal of Pharmacology June 1, 1983
- Ketamine use: a review Addiction July 21, 2011
- From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs. Drug Testing and Analysis 2014
- A Review of the Nonmedical Use of Ketamine: Use, Users and Consequences Journal of Psychoactive Drugs December 1, 2000
and 7 more in the library