Plugs the ion channel pore of the receptor at the phencyclidine (PCP) binding site
The strength of an NMDA receptor antagonist is described as “trapping” behavior, i.e., how likely it is to become lodged in the pore, leading to prolonged inhibition of calcium influx into the neuron
➔ protects against excitotoxicity in conditions of excessive glutamate release, but may contribute to NMDA receptor hypofunction → elevated KYNA is associated with schizophrenia
Drugs with this mechanism (16)
Amantadine — NMDA antagonist with uncertain dopaminergic actions; used for Parkinson symptoms and levodopa dyskinesia.
Dextromethorphan — OTC cough suppressant; NMDA antagonist and sigma-1 agonist, dissociative in overdose.
Dextrorphan — Dextromethorphan's active metabolite; the NMDA antagonism behind both the dissociative effect and the abuse potential.
Dizocilpine — MK-801; the prototypical potent NMDA channel blocker (research).