Posted by Shawn. T. on August 28, 2005, at 14:51:06
In reply to Re: Are all NMDA antagonists neurotoxic ?, posted by Mistermindmasta on August 27, 2005, at 23:35:22
I don't believe that NMDA antagonism "burns out" dopamine or serotonin receptors. Farber et al. (2002) have suggested that NMDA antagonists disinhibit inhibitory GABA neurons in subcortical areas that modulate other neurons that release glutamate and acetylcholine into the cerebral cortex (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11803444&dopt=Abstract). They also suggested that the simultaneous activation of M3 muscarinic acetylcholine receptors and AMPA/kainate glutamate receptors in the cerebral cortex is involved in NMDA antagonist neurotoxicity. Initially, the neurotoxicity occurs in the retrosplenial cortex and posterior cingulate, but much higher doses may affect other regions of the cortex.
No one has ever shown that dextromethorphan or memantine causes NMDA antagonist neurotoxicity. A serotonin reuptake inhibitor, fluoxetine, inhibits the development of NMDA antagonist neurotoxicity in the rat brain (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10812043&dopt=Abstract). So it could be the case that the serotonin reuptake inhibition caused by dextromethorphan prevents the drug from inducing neurotoxicity; however, this will remain speculation until someone actually examines dextromethorphan's potential for neurotoxicity.
Shawn
poster:Shawn. T.
thread:546405
URL: http://www.dr-bob.org/babble/20050827/msgs/547663.html