Posted by Chairman_MAO on August 30, 2005, at 10:03:16
In reply to Are all NMDA antagonists neurotoxic ?, posted by linkadge on August 27, 2005, at 9:51:50
They are neuroprotective--against neurotox caused by excessive glutaminergic activity . The problem is that there is a "downstream" neurotoxicity associated with their neurprotecitve mechanism--it has to do with the induction of something called HSP (heat shock protein) 70 which I believe ultimately leads to apoptosis if the cell cannot recover normal functioning. This could be mediated by Read William White's "this is your brain on dissociatives" for a detailed explanation of this mechanism. I am not sure if the rest of the document holds water, though.
BTW, the jury is still out as to whether this even occurs in humans. At any rate, the strenght of the blockade caused by therapeutic concentrations of memantine I believe is too weak to cause neurotoxicity. Also, this neurotoxicity in animals likely has something to do with NDMA antagonism preventing normal GABAergic inhibition; thus, benzodiazepines and gabanergic drugs (such as muscimol) prevent the neurotoxicity. Many, many agents can do this via various means: a2 agonists, LSD (seriously), BZDs, clozapine (IIRC), etc.
poster:Chairman_MAO
thread:546405
URL: http://www.dr-bob.org/babble/20050827/msgs/548670.html