Journal
CURRENT NEUROPHARMACOLOGY
Volume 14, Issue 2, Pages 200-209Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1570159X14666151113123221
Keywords
Dementia; glutamate; kynurenic acid; memantine; neuroprotection; NMDA
Categories
Funding
- Hungarian Brain Research Program (NAP) [KTIA_13_NAP-A-III/9, KTIA_13_NAP-A-II/17]
- EUROHEADPAIN [602633, FP7-Health 2013-Innovation]
- OTKA [K105077]
- MTA-SZTE Neuroscience Research Group of the HungarianAcademy of Sciences
- University of Szeged
- [TAMOP-4.2.2.A-11/1/KONV-2012-0052]
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Glutamatergic neurotransmission, of special importance in the human brain, is implicated in key brain functions such as synaptic plasticity and memory. The excessive activation of N-methyl-D-aspartate (NMDA) receptors may result in excitotoxic neuronal damage; this process has been implicated in the pathomechanism of different neurodegenerative disorders, such as Alzheimer's disease (AD). Memantine is an uncompetitive antagonist of NMDA receptors with a favorable pharmacokinetic profile, and is therefore clinically well tolerated. Memantine is approved for the treatment of AD, but may additionally be beneficial for other dementia forms and pain conditions. Kynurenic acid (KYNA) is an endogenous antagonist of NMDA receptors which has been demonstrated under experimental conditions to be neuroprotective. The development of a well-tolerated NMDA antagonist may offer a novel therapeutic option for the treatment of neurodegenerative disease and pain syndromes. KYNA may be a valuable candidate for future drug development.
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