NEW THERAPEUTIC PERSPECTIVES WITH LOW-AFF INITY NMDA RECEPTOR ANTAGONISTS

Glutamate receptor antagonists with selective action at the N-methyl-D -aspartate (NMDA) receptor are promising agents for the neuroprotectiv e and symptomatic pharmacotherapy of various neuropsychiatric disorder s. Although NMDA receptor antagonists of the phencyclidine (PCP) type are precluded from clinical use because of their psychotomimetic prope rties, amantadine and memantine have been administered to human patien ts with idiopathic Parkinson's disease and spasticity for many years w ithout serious adverse effects. The mechanisms underlying these differ ences in psychotogenicity of different NMDA receptor antagonist are cu rrently being discussed. Different affinity to the PCP binding site of the NMDA receptor, region-specific pharmacology, as well as different binding profiles to neurotransmitter receptors other than the NMDA ty pe glutamate receptor, most likely play a role in determining whether an NMDA receptor antagonist drug will be tolerated clinically or not.