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mechism of action of norepinephrine selective ADs

Posted by John Doughboy on May 13, 2008, at 13:59:44

I've only ever used SSRI (or low dose SNRI) as antidepressants, and I basically understand how they work. The massive amounts of serotonin in the synapses from the uptake pump being blocked lets all that serotonin hit the post synaptic receptors. After several weeks, different sub- types of these receptors upregulate or downregulate (becoming more or less sensitive,respectively) Some receptors, like many of the sub-types of the 5HT-1 upregulate,which helps with anxiety and whatnot. Much of the 5HT-2 downregulate,which can be seen as a good think because it helps with obsessions in OCD, and a bad thing because it may be responsible for some of the sexual side effects and it may act as a hetero receptor so that less dopamine releases downstream.

I know it's way more complicated than that and I'm leaving all kinds of things out like "the neurogenesis theory", but you get the point.

How the hell do norepinephrine reuptake blocking meds work? I hear they are good for people who need more drive,motivation,and energy, but I don't see how they do that. Do they just leave so much extra NE hanging around that all the NE receptors downregulate over time and become less sensitive? That would make sense because they are used for anxiety and some people even claim they make them slightly sleepy,but how does that work for motivation and anhedonia and stuff like that? Do these meds make more dopamine available downstream after chronic dosing or anything like that?

Someone please explain this to me. I'm starting Wellbutrin and the dopamine component of that med I won't even get started on. It just seems like any other drug like that(methylphenidate,amphetamine) would just decrease dopamine over time.

Are there NE and DA sub-types that have different (opposing) properties like the serotonin system?

Please help me understand how NE/DA ADs work!


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poster:John Doughboy thread:828908
URL: http://www.dr-bob.org/babble/20080510/msgs/828908.html