John - short answer: no, I've done no research on memantine (which is an uncompetitive NMDA receptor antagonist in the same general class as MK-801, phencyclidine, ketamine).
Long answer...
I am somewhat familiar - though at least 6 months out of date - with a parallel, relevant area: the field of nitric oxide research. Neurotransmission by the amino acid glutamate (through the NMDA receptor) activates the inducible form of nitric oxide synthase (i.e. iNOS) via a route under intense investigation. Activation of iNOS leads to the synthesis of nitric oxide (NO), a potentially toxic gas, which can freely diffuse out of (and in to) cells.
High levels of glutamate - for example, those which occur during ischemic events - induce the generation of high levels of NO; this gas is the primary culprit for the observed damage in 'ischemia-reperfusion neurotoxicity' (see ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10800947&dopt=Abstract). Interestingly, this glutamate-NO duo is probably a critical molecular substrate in learning: there is substantial evidence that when a presynaptic neuron releases physiological (read: normal) levels of glutamate, the 'receiving' (postsynaptic) neuron will release moderate levels of NO. In this case the NO acts as a 'retrograde messenger', telling the presynaptic cell, 'Message received. Let's develop this relationship further'. While it is believed NO plays an important role in establishing the strength of interactions between neurons - the neural basis for learning - the actual means by which this is accomplished is poorly understood.
This is a very long way of getting to my point: when ever I read claims like you've listed, I run. There is a 99.999% chance against that any one transmitter system could be the sole critical mediator in all those neuropathologies. In fact the odds are close to the same against the idea that any one transmitter is critical in any ONE of those diseases. Moreover, in the case of the NMDA receptor, the observed effects of blocking this system are much more likely due to the effects on iNOS induction rather than blocking glutamate's action per se.
The other reason I don't like those magic bullet type of claims is that they leave out the very real likelihood of toxicity. For example, I've described above the role of glutamate/NMDA/NO in learning. Broadly speaking, there's nothing in a NMDA receptor antagonist that allows it to distinguish between beneficial actions (blocking glutamate toxicity in the pathological brain) from deleterious actions (blocking glutamate neurotransmission in the pathological brain).
In short (!), don't buy the hype.
Scott |
