Synaptic communication and re-uptake / reuptake inhibitors / Adrafinil

r norman rsn_ at _comcast.net
Thu Dec 16 20:22:26 EST 2004


On Thu, 16 Dec 2004 23:14:03 +0100, 1234 <123412 at 101.com> wrote:

>INFOHAZARD wrote:
>> 
>>>Also how could things like Adrafinil (norepinephrine agonist) work? Is 
>>>it stored in vesicules at the end of axons together with the 
>>>norepinephrine and released into the synapses together with it?
>>>
>> [...]
>> Not stored.  Diffusion.  Diffusion. OK?
>
>Explain "diffusion" to a layman please?
>
>Does it leak out of the brain vessels and spreads into all the synaptic 
>clefts roughly equally? (I don't know how this could be helpful: seems 
>to add just random "noise" to brain signals...?)
>
>...and then is it reabsorbed in the vessels when the concentration of 
>the agonist in the vessel becomes lower (liver has worked) than the 
>concentration in the synaptic clefts?
>

When you take any drug, whether by pill or by injection or whatever,
usually the stuff ends up in the blood stream and is carried to all
the organs and tissues.  There it diffuses through the capillaries
into the extracellular fluid (I am deliberately ignoring the details
of capillary exchange -- filtration and reabsorption).  That way it is
available at roughly the same concentration to all the cells of the
body.

Brain tissue is somewhat different because of the blood-brain barrier.
However any drug that is active in the CNS is capable of crossing that
barrier.  Still, the net effect is the same -- diffusion from the
circulatory system through the extracellular fluid distributes
relatively uniformly to all cells.

As the drug is eliminated in some way -- taken up by some specific
tissues and metabolized or filtered in the kidney -- its concentration
in the general body fluids drops.  Again, this is usually a relatively
uniform process across the entire body.

Details vary, sometimes substantially, for particular drugs and
particular organs. Hence the big research effort in pharmacokinetics,
the study of all this.






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