Posted by linkadge on February 7, 2010, at 18:22:36 [reposted on February 22, 2010, at 1:21:06 | original URL]
In reply to Re: To make it more complicated. .. linkadge, posted by Mikez on February 7, 2010, at 10:48:23
>Linkadge , when you say if one responds to >stimulants they are not necessarily a dopamine >responder is that because stimulants work on >other transmitters (ie Nora) as you said >earlier?
l-dopa is an option, but I'm not exactly sure if it works like tyrosine (ie a precursor to norepinephrine as well). Selegeline is preferential to MAO-B. Contrary to popular believe MAO-B does not readily metabolize dopamine. MAO-A inhibitors have a much stronger effect on dopamine metabolism than MAO-B inhibitors. MAO-B preferentially demeniates phenylethylamine or PEA. The issue is complicated as selegiline is metabolized into (meth?)amphetamine. PEA and amphtetamine have similar actions.
Dopamine agonist are selective to certain dopamine receptors. Some (such as mirapex) have activity at 5-ht1a 5-ht2b and other receptors - thus they are not selective to dopamine receptors. Furthermore because they affect certain dopamine receptors more than others, their effect would not mimic an overall increase or decrease in dopamine. Also mirapex appears to have an ability to increase BDNF (seeminly independant of its dopamine agonist activity). This may be responsible for its antidepressant effect, and not the dopamine agonist effect.
Another issue is that the dopamine transporter has the ability to reabsorb serotonin as well. When SSRI's are adminstered, the dopamine transporter appears to reabsorb more serotonin than usual. So, perhaps augmentation of an SSRI with a DAT inhibitor actually exerts its effect by preventing DAT from eating serotonin.
This is an alternate explaination for why SSRI's poop out. Perhaps instead of squelching dopamine, the drugs poop out because the dopamine transporter starts to reuptake the extra serotonin and so the theraputic serotonin enhancing effect is lost.
So to answer your question, I don't know. Its so friggen complex and thats the point I am trying to make. Neurotransmitters do not exist in a vaccum. You cannot alter one without altering them all. Response to a drug does not mean anything more than response to a drug.Linkadge
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URL: http://www.dr-bob.org/babble/neuro/20091104/msgs/937647.html