[New therapeutic possibilities with low-affinity NMDA receptor antagonists].
Glutamate receptor antagonists with selective action at the N-methyl-D-aspartate (NMDA) receptor are promising agents for the neuroprotective and symptomatic pharmacotherapy of various neuropsychiatric disorders. Although NMDA receptor antagonists of the phencyclidine (PCP) type are precluded from clinical use because of their psychotomimetic properties, amantadine and memantine have been administered to human patients with idiopathic Parkinson's disease and spasticity for many years without serious adverse effects. The mechanisms underlying these differences in psychotogenicity of different NMDA receptor antagonist are currently 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 type glutamate receptor, most likely play a role in determining whether an NMDA receptor antagonist drug will be tolerated clinically or not.
Kornhuber
J
J
Psychiatrische Klinik, Universität Würzburg.
Weller
M
M
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D000547:Amantadine / Q000009:adverse effects / Q000627:therapeutic use*; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D005973:Glutamine / Q000502:physiology; D006801:Humans; D008559:Memantine / Q000009:adverse effects / Q000627:therapeutic use*; D016202:N-Methylaspartate / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D017478:Receptors, Phencyclidine / Q000037:antagonists & inhibitors / Q000502:physiology
D000978:Antiparkinson Agents; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D017478:Receptors, Phencyclidine; D005973:Glutamine; D016202:N-Methylaspartate; D000547:Amantadine; D008559:Memantine
Neue therapeutische Möglichkeiten mit niederaffinen NMDA-Rezeptorantagonisten.