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Re: Atomoxetine: NMDA receptor antagonist undopaminergic

Posted by linkadge on July 25, 2020, at 10:09:06

In reply to Re: Atomoxetine: NMDA receptor antagonist, posted by undopaminergic on July 25, 2020, at 7:11:28

Yes typo. Angel dust.

>Can you clarify that? I don't think you mean >glutamate protects neurons.

Right. Glutamate, which is critical for proper neurotransmission in a certain concentration range, can become neurotoxic at elevated concentrations. You are correct in saying that NMDA antagonists, block glutamate receptors, but the net effect is a reduction in 'glutamate neurotransmission' (usually - at least in lower doses). However, as the concentration increases other things begin to happen. I haven't read enough on this topic, but I understand blocking NMDA can increase dopamine (hence the application of amantadine in Parkinson's). At certain doses, drugs like PCP and ketamine can increase glutamate release. I'm not sure of the mechanism here (AMPA receptors or GABA inhibition or something). I'm not sure too, if there are NMDA autoreceptors which try to offset the NMDA blockade. I'm not sure if this is homeostatic, or if it results in a net *increase* in glutamate neurotransmission. Increasing glutamate may be part of the antidepressant effect. I know that some of the neurogenic properties of ketamine require a glutamate increase, which can trigger BDNF. Acute lithium often has antidepressant effects. In the short term, lithium decreases glutamate reuptake (increasing glutamate) over time (perhaps as BDNF levels rise) glutamate reuptake is actually enhanced (more stabilizing). It's very complex. In some cases, reducing glutamate improves depression, in other cases, increasing it does. Of course, much of it is region specific. Some studies have tried combinations of NMDA antagonists and NMDA agonists (i.e. d-cycloserine). See below for the use of d-cycloserine to prolong the antidepressant effect of ketamine. Very strange.

https://www.nature.com/articles/s41386-019-0480-y#:~:text=D%2Dcycloserine%20(DCS)%2C,as%20a%20depression%20augmentation%20treatment.

Linkadge



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