Posted by Mistermindmasta on August 27, 2005, at 23:35:22
In reply to Are all NMDA antagonists neurotoxic ?, posted by linkadge on August 27, 2005, at 9:51:50
> Without delving much into the subject, I have read some article headlines about the neurotoxicity of NMDA antagonists.
> Could somebody tell me if this is an effect of all NMDA antagonists or just certain ones. Or is it a result of overdosing on an NMDA antagonist.
> What is the mechanism anyway, I thought NMDA antagonists were neruoprotective ?
As I understand it, DXM could be an antidepressant by lowering the activity of glutamate, thus preventing glutamate induced neurotoxicity - a key step to depression. Therefore, neurogenesis is allowed to occur and activity in many areas of the brain improves due to increased connectivity. However, more doesn't necessarily equal better and the problem with depression might not actually lie in too much glutamate - too much glutamate might just be a symptom or an effect of whatever really causes depression. The problem you run into is this - indeed, NMDA antagonists can be neuroprotective, but when you antagonize it too much, you start to run into problems because too much antagonism can burn out dopamine receptors and maybe serotonin receptors, from too much activity there. The NMDA receptor has a U curve kinda thing going on - too much glutamate causes cell death, just the right amount and cells thrive, and too little and you see to run into problems of neurotoxicity from dopamine, not glutamate. Also, schizophrenia is thought to arise partially from underactive NMDA receptors. So many the guy had an acute psychotic episode from this whole self medication thing. Or, he abruptly stopped using DXM... which obviously could have many bad effects.