Ephenidine

Ephenidine (N-ethyl-1,2-diphenylethylamine, NEDPA) is a diarylethylamine dissociative and an antagonist of the NMDA glutamate receptor. Like ketamine, PCP and its close relative diphenidine it is an open-channel blocker: it enters the receptor's ion channel once glutamate has opened it and binds within the pore at the PCP / MK-801 site, blocking cation flux in a use- and voltage-dependent way. In [³H]-MK-801 binding it is a potent inhibitor (Ki ≈66 nM), and electrophysiology shows a ketamine-like, voltage-dependent block of NMDA-receptor currents. Blocking NMDA signalling in cortical and thalamic circuits produces the dissociative state: analgesia, detachment from body and environment, disordered sensory integration and, at higher doses, anaesthesia. It is not fully selective: alongside the NMDA receptor it shows modest affinity for the dopamine (Ki ≈379 nM) and noradrenaline (≈841 nM) transporters and for σ1 (≈629 nM) and σ2 (≈722 nM) sites, which may add a mild stimulant/psychotomimetic colour to its effects. Ephenidine has a single stereocentre and is used as the racemate. Human pharmacokinetics are poorly defined because it exists only as an unapproved research chemical. It is extensively metabolised in the liver (N-dealkylation and aromatic hydroxylation), and users report a moderate-to-long duration typical of the diarylethylamine dissociatives.