Editing NMDA receptor (section)

==== Memantine and related compounds ====
[[File:Memantine and amantadine.jpg|thumb|right|300px|'''Figure 5:''' Chemical structures of memantine (right) and amantadine (left)]]
Because of these adverse side effects of high affinity blockers, the search for clinically successful NMDA receptor antagonists for neurodegenerative diseases continued and focused on developing low affinity blockers. However the affinity could not be too low and dwell time not too short (as seen with Mg<sup>2+</sup>) where membrane depolarization relieves the block. The discovery was thereby development of uncompetitive antagonist with longer dwell time than Mg<sup>2+</sup> in the channel but shorter than MK-801. That way the drug obtained would only block excessively open NMDA receptor associated channels but not normal neurotransmission.<ref name="Lipton2" /><ref name="Sonkusare" /> Memantine is that drug. It is a derivative of amantadine which was first an anti-influenza agent but was later discovered by coincidence to have efficacy in Parkinson's disease. Chemical structures of memantine and amantadine can be seen in figure 5. The compound was first thought to be [[dopaminergic]] or [[anticholinergic]] but was later found to be an NMDA receptor antagonist.<ref name="Dominguez" /><ref name="Lipton2" />

Memantine is the first drug approved for treatment of severe and more advanced [[Alzheimer's disease]], which for example anticholinergic drugs do not do much good for.<ref name="Sonkusare" /> It helps recovery of synaptic function and in that way improves impaired memory and learning.<ref name="Koch" /> In 2015 memantine is also in trials for therapeutic importance in additional neurological disorders.<ref name="Lipton3">{{cite journal | vauthors = Lipton SA | title = Pathologically activated therapeutics for neuroprotection | journal = Nature Reviews. Neuroscience | volume = 8 | issue = 10 | pages = 803–808 | date = October 2007 | pmid = 17882256 | doi = 10.1038/nrn2229 | s2cid = 34931289 }}</ref>

Many second-generation memantine derivatives have been in development that may show even better neuroprotective effects, where the main thought is to use other safe but effective modulatory sites on the NMDA receptor in addition to its associated ion channel.<ref name="Lipton3" />