What's the difference between an SSRI and a seretonin receptor agonist?

Question

As far as I can ascertain, drugs like Buspiron, activate serotonin receptors, mimicking the effect of the neurotransmitter. And, SSRIs increase the extracellular level of the neurotransmitter serotonin by inhibiting its reuptake into the presynaptic cell. So, presumably, the end result of both is an increase in the level of available seretonin.

Perhaps, with SSRI's, the increased level is due to inhibition while with seretonin receptor agonists, it results from activation. Is that correct? Is there some other main difference I'm just not getting, here?

Thanx for any and all help :-) :-).

Answer 1

Good Q, I Suspect it is Ultimately "Compartmentalization", Which is to Say, You Want Serotonin to Increase Only In the CNS.

Answer 2

If the receptor is not active, then what is there to receive the serotonin (seretonin)? Levels and receptivity for those levels is not the same thing, i.e. zero receptivity, zero serotonin symptomotology at 100% serotonin saturation.

Answer 3

You ask very good questions, and let me put it this way.  In theory, both an agonist and an uptake blocker will produce the same effect, i.e. stimulation of the receptor. In fact, many consider uptake blockers to be "indirect agonists".  However, when you inhibit uptake, you still have the endogenous transmitter which can be metabolized by endogenous enzymes, many of which are specific for that transmitter.  In the case of serotonin, you have MAO as the main enzyme.  With the man-made agonists, like Buspiron, these are generally not metabolized in the brain.  They are metabolized by liver enzymes, but many times it is the metabolite that is the active agonist. Also, SSRI's are not really that selective, as most of them also inhibit the uptake of norepinephrine.  Side effects will have a bearing as well.

Answer 4

An agonist is a molecule that functions as a mimic to the original neurotransmitter, like serotonin.  An SSRI actually increases the levels of the native molecule by blocking its clearance from the synapse.  Both have their effects and side-effects by over-stimulation of serotonin receptors, along with cross-reactivity with other pathways.

Answer 5

Well... there are psychotropics that stimulate and/or simulate the production of certain neurotransmitters; as well as meds that inhibit or stimulate it's uptake.  You've really stated it effectively in a brief manner.

Answer 6

As Dr. Ben has already said, SSRIs function by reducing the reuptake of serotonin from the synapse, ultimately making more available for postsynaptic reception.  Drugs like Buspiron do serve as serotonin agonists, literally functioning as serotonin at the postsynaptic site.  Thus, in a sense they do the same thing - increase the rate of reception on the postsynaptic membrane.  

The differences, unfortunately, lie in the next level of complexity in the serotonergic system.  As you may know, serotonin is has major effects throughout the brain.  What you may not know, however, is that serotonergic tracts take up a relatively small portion of actual tissue.  Only 200,000 of the 100 billion neurons in the brain are serotonergic.  The location and function of each of these neurons is further differentiated by what kind of serotonin receptors are present.  To date, we know of at least 15 different 5HT receptors.  Different drugs effect different serotonin receptors.  Thus, although their net effect on extracellular serotonin at a particular synapse may be similar, SSRIs and serotonin agonists may still have very different effects.