Memantine: targeting glutamate excitotoxicity in Alzheimer's disease and other dementias.
The management of dementia has changed since the development of new antidementia drugs. The benefits observed in Alzheimer's disease (AD) with selective cholinergic transmission treatments are mainly symptomatic, without clear evidence of neuroprotection. The hypothesis that glutamate-mediated neurotoxicity is involved in the pathogenesis of AD is finding increasingly more acceptance in the scientific community. Glutamate receptors are overactive, and N-methyl-D-aspartate (NMDA) receptor antagonists have therapeutic potential for the treatment of AD and other neurological disorders. Memantine is a noncompetitive NMDA antagonist that is considered a neuroprotective drug. Memantine's capacity has been demonstrated in preclinical studies, and it is considered a useful symptomatic treatment for AD. Memantine has been shown to benefit cognition, function, and global outcome in patients with moderate to severe AD, and it is currently approved by the US Food and Drug Administration (FDA) for the treatment of moderate to severe AD. Recently, memantine has also demonstrated efficacy in the initial stages of AD, although FDA authorization is pending. This review highlights the important pharmacological and clinical aspects of memantine, as well as some basic mechanisms mediating glutamatergic neurodegeneration.
Molinuevo
José L
JL
Unitat Memoria-Alzheimer, Institut Clinic Malalties del Sistema Nerviós, Hospital Clinic i Universitari, Barcelona, Spain.
Lladó
Albert
A
Rami
Lorena
L
D027322:Amino Acid Transport System X-AG; D000818:Animals; D002986:Clinical Trials as Topic; D003704:Dementia / Q000188:drug therapy* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008559:Memantine / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015394:Molecular Structure; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism
D027322:Amino Acid Transport System X-AG; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D008559:Memantine