NMDA receptor antagonists. A new therapeutic approach for Alzheimer's disease.
Research into Alzheimer's disease (AD) pathology has identified several underlying disease processes that are potential targets for drug discovery and development. One strategy targets glutamatergic neurotransmission mediated by the N-methyl-D-aspartate (NMDA) receptor. Therapeutic intervention with high-affinity NMDA receptor antagonists, such as phencyclidine (PCP) and MK-801, is not practical due to adverse side effects; however, a low-moderate affinity, uncompetitive and strongly voltage-dependent NMDA receptor antagonist, memantine (NamendaTM), is well tolerated and recently has been approved by the U.S. Food and Drug Administration for the treatment of moderate to severe AD. Clinical results support NMDA receptor antagonism as a viable therapeutic strategy for AD and suggest that this novel pharmacologic approach, either alone or in combination with other drugs, is likely to significantly impact the current AD treatment paradigm.
Farlow
Martin R
MR
Department of Neurology, Indiana University School of Medicine, Indianapolis, USA.
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D018450:Disease Progression; D000077265:Donepezil; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use; D008559:Memantine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D002800:Cholinesterase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D007189:Indans; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D000077265:Donepezil; D008559:Memantine