Key binding interactions for memantine in the NMDA receptor.

Article Details

Citation

Limapichat W, Yu WY, Branigan E, Lester HA, Dougherty DA

Key binding interactions for memantine in the NMDA receptor.

ACS Chem Neurosci. 2013 Feb 20;4(2):255-60. doi: 10.1021/cn300180a. Epub 2012 Dec 7.

PubMed ID
23421676 [ View in PubMed
]
Abstract

Memantine (Namenda) is prescribed as a treatment for moderate to severe Alzheimer's Disease. Memantine functions by blocking the NMDA receptor, but the key binding interactions between drug and receptor are not fully elucidated. To determine key binding interactions of memantine, we made side-by-side comparisons of IC(50) for memantine and amantadine, a structurally related drug, in the GluN1/GluN2B NMDA receptor. We identified hydrophobic binding pockets for the two methyl groups on memantine formed by the residues A645 and A644 on the third transmembrane helices of GluN1 and GluN2B, respectively. Moreover, we found that while adding two methyl groups to amantadine to produce memantine greatly improves affinity, adding a third methyl group to produce the symmetrical trimethylamantadine diminished affinity. Our results provide a better understanding of chemical-scale interactions between memantine and the NMDA channel, which will potentially benefit the development of new drugs for neurodegenerative diseases involving NMDA receptors.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
MemantineGlycine receptors (Protein Group)Protein groupHumans
Unknown
Inhibitor
Details