Clinical doses of atomoxetine significantly occupy both norepinephrine and serotonin transporters

[nanonug]

Well, it seems Strattera (atomoxetine) may be a SNRI after all: Clinical doses of atomoxetine significantly occupy both norepinephrine and serotonin transporters (NET and SERT): Implications for treatment of depression and ADHD.

 

[anciendaze]

If you have followed some posts I have made on prescription drugs you should know this kind of unexpected finding is very common. Most approved drugs have several kinds of actions beyond listed indications. This is most striking when you find psychotropic drugs with antibacterial or antiviral activity, as in the case of fluoxetine. This brings us full circle from the first discoveries of antidepressant action in drugs intended to treat TB.

There is a more serious confusion over the role of receptors targeted by drugs. Few have only one specific function. About 90% of serotonin receptors are outside the brain. Within the brain, about 90% of serotonin receptors are typically inactivated by glial blockade. (Glial cells sit over these receptors on neurons, preventing them from functioning in synapses. In extreme cases synaptic stripping caused by intruding glia is associated with neurological degeneration.)

I have suspicions that common SNRIs also have antiviral activity. At this stage the research literature is confusing. Let me know if you run across an example. This might give us a clue about what doctors have actually been treating with them.

Receptors not only handle chemical signals between neurons and identify pathogens, they also facilitate communication between cells of the immune system. The effects of common drugs on these signals are little known.

 

[Valentijn]

It still looks like the effect on serotonin isn't nearly as strong as the effect on norepinephrine.

I'm also curious why the vast majority of trycyclics, SSRIs, NRIs and SNRIs cause low blood pressure and only a couple raise it.

 

[anciendaze]

It still looks like the effect on serotonin isn't nearly as strong as the effect on norepinephrine.

I'm also curious why the vast majority of trycyclics, SSRIs, NRIs and SNRIs cause low blood pressure and only a couple raise it.

Serotonin, norepinephrine and dopamine are all biochemically related to the 5HTT synthesis pathway. It is very hard to directly affect a single one alone. A look at the chemical structures should make this plausible. Regulation of blood pressure is one immediate effect of most monoamine neurotransmitters.

Even the antidepressants you do not mention, MAOIs, cause orthostatic hypotension, which can result in syncope (fainting) on standing due to "low blood pressure". This despite the prominent warnings that MAOIs can result in a "hypertensive crisis", a sudden attack of "high blood pressure", when combined with common foods like cheese. The problem is an introduced defect in regulating blood pressure, not specifically raising or lowering it. While syncope can be dangerous, because of falls, it is less emphasized than hypertension, because of the associated danger of stroke. Combining any of the classes of antidepressants you mention with MAOIs can result in hypertensive crises, despite their common effect of lowering blood pressure.