N-methyl D-aspartate (NMDA) receptor antagonists and memantine treatment for alzheimer's disease, vascular dementia and parkinson's disease

David Olivares, Varun K. Deshpande, Ying Shi, Debomoy Lahiri, Nigel H. Greig, Jack T. Rogers, Xudong Huang

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Memantine, a partial antagonist of N-methyl-D-aspartate receptor (NMDAR), approved for moderate to severe Alzheimer's disease (AD) treatment within the US and Europe under brand name Namenda (Forest), Axura and Akatinol (Merz), and Ebixa and Abixa (Lundbeck), may have potential in alleviating additional neurological conditions, such as vascular dementia (VD) and Parkinson's disease (PD). In various animal models, memantine has been reported to be a neuroprotective agent that positively impacts both neurodegenerative and vascular processes. While excessive levels of glutamate result in neurotoxicity, in part through the over-activation of NMDARs, memantine-as a partial NMDAR antagonist, blocks the NMDA glutamate receptors to normalize the glutamatergic system and ameliorate cognitive and memory deficits. The key to memantine's therapeutic action lies in its uncompetitive binding to the NMDAR through which low affinity and rapid off-rate kinetics of memantine at the level of the NMDAR-channel preserves the physiological function of the receptor, underpinning memantine's tolerability and low adverse event profile. As the biochemical pathways evoked by NMDAR antagonism also play a role in PD and since no other drug is sufficiently effective to substitute for the first-line treatment of L-dopa despite its side effects, memantine may be useful in PD treatment with possibly fewer side effects. In spite of the relative modest nature of its adverse effects, memantine has been shown to provide only a moderate decrease in clinical deterioration in AD and VD, and hence efforts are being undertaken in the design of new and more potent memantine-based drugs to hopefully provide greater efficacy.

Original languageEnglish
Pages (from-to)746-758
Number of pages13
JournalCurrent Alzheimer Research
Volume9
Issue number6
StatePublished - Jul 2012

Fingerprint

Memantine
Vascular Dementia
N-Methyl-D-Aspartate Receptors
Vascular Diseases
Parkinson Disease
Alzheimer Disease
Memory Disorders
Glutamate Receptors
Levodopa
Neuroprotective Agents
Pharmaceutical Preparations
Names
Blood Vessels
Glutamic Acid

Keywords

  • Alzheimer's disease
  • Amantadine
  • Memantine
  • Nmdar
  • Parkinson's disease
  • Vascular dementia

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

N-methyl D-aspartate (NMDA) receptor antagonists and memantine treatment for alzheimer's disease, vascular dementia and parkinson's disease. / Olivares, David; Deshpande, Varun K.; Shi, Ying; Lahiri, Debomoy; Greig, Nigel H.; Rogers, Jack T.; Huang, Xudong.

In: Current Alzheimer Research, Vol. 9, No. 6, 07.2012, p. 746-758.

Research output: Contribution to journalArticle

Olivares, David ; Deshpande, Varun K. ; Shi, Ying ; Lahiri, Debomoy ; Greig, Nigel H. ; Rogers, Jack T. ; Huang, Xudong. / N-methyl D-aspartate (NMDA) receptor antagonists and memantine treatment for alzheimer's disease, vascular dementia and parkinson's disease. In: Current Alzheimer Research. 2012 ; Vol. 9, No. 6. pp. 746-758.
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