Posted by Mitch on July 9, 2001, at 13:30:49
In reply to Re: Going Crazy: Could it be Buspar????? Mitch, posted by AMenz on July 9, 2001, at 10:52:07
> Let's take this a step at a time. Please help me here.
> "Buspirone (0.01-2.5 mg/kg, s.c.) dose-dependently decreased dialysate levels of serotonin (-50%), and increased those of dopamine (+100%) and noradrenaline (+140%)."Well, for starters I didn't write the thing! It appears they are administering buspirone to mice/rats and then seeing what happens to the extracellular neurotransmitters in their brains in response to the administration.
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> Also what is WAY 100,635 and why are they mentioning it here if they are doing a comparison of fluoxetine and buspirone alone and in combination?It is an investigational drug that has very specific actions that they can use as a comparison/control. I think most meds have their beginning named like that until they are further developed. When this article was written there was a lot of success stories about augmenting SSRI antidepressants with buspirone and I think their findings here (and other people's anecdotal findings with humans)is the reason for the comparison of buspirone alone and with fluoxetine. I am sensitive to AD's and I was taking an SSRI at the time (Celexa), and it sure boosted it alright!
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> "The reduction by buspirone of serotonin levels was abolished by the serotonin1A receptor antagonist, WAY 100,635 (0.16), which did not, however, modify its influence upon dopamine and noradrenaline."The investigational drug WAY... when given along with buspirone kept buspirone from reducing serotonin levels (blocked Buspar's anti-serotonin activity). But buspirone still boosted dopamine and norepinephrine levels despite that.
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> Next fluoxetine increases extracellelar levels of serotonin:Prozac is an SSRI drug that blocks the "pumps" that take extra serotonin in the synapses and removes it. If you block the pump that removes the serotonin from the synapse then it accumulates to a higher level-that is basically how SSRi's are supposed to work (from what I understand).
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> "In contrast to buspirone, the serotonin reuptake inhibitor, fluoxetine (10.0), increased frontocortical levels of serotonin (+ 120%), dopamine (+55%) and noradrenaline (+90%)."That is just the result of Prozac being admininstered alone (the extra-cellular concentrations of the three neurotransmitters mentioned). Obviously there are boosts in other transmitters besides serotonin due to fluoxetine.
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> Together Buspirone reduces the serotonin levels as enhanced alone by fluoxetine:Buspirone simply thwarts or reverses the serotonin increase that fluoxetine causes.
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> "Buspirone dose-dependently (0.01-2.5) decreased the induction by fluoxetine of serotonin levels yet potentiated (three-fold) its elevation of dopamine and noradrenaline levels."The trick here is that when buspirone was coadministered with Prozac you get a *potentiation* of dopamine and norepinephrine. That wouldn't have happened if you just administered Prozac.
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> But then you come to the agonist properties of buspirone at the serotonin1A receptor. What does this entail? Does it increase certain intracellular activity because it mimics seratonin so that the cell acts as if seratonin were enhanced instead of diminished?That sounds like a plausible explanation-better than what I could have conjectured. Perhaps *synthesis* of serotonin is also decreased as a result. Possible analogy?? (it seems like we got plenty why make more??)
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> "In conclusion, the inhibitory influence of buspirone upon resting and fluoxetine-stimulated serotonin levels reflects its agonist properties at serotonin1A autoreceptors. The facilitatory influence of buspirone upon resting and fluoxetine-stimulated dopamine and noradrenaline levels may also involve its serotonin1A properties."Good question. I can see I think how it can reduce serotonin-but there is some extra hidden complexity (of course) that explains the NE and DA boost.
> OK so my questions in closing are:
>
> 1)what is the consequence of this mimicking effect.It reduces jitteriness (less serotonin)-which is what happens during startup of taking SSRi's-you get all restless and jittery (lots of extra serotonin until your receptor density changes -from what I have read here anyway).
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> 2) more seratonin equals more mania and less seratonin depressionQuite possibly.
Personally, I think it has more to do with the relative balance between the neurotransmitters. Some people respond better to certain AD's better than others. Basically, I think that pitching in Buspirone with an SSRi-turns the combination into more of an Effexor-like response. I have become hypomanic on very selective SSRi's (at higher doses), while a tiny dose of Effexor can make me very hypomanic.
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> 3) do they have any idea as to effect of dopamine and noradrenaline on mood?Well, from what my pdoc has mentioned (very generally), dopamine is involved with interest and Norepi with drive and energy. Serotonin has the most to do with "mood".
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> Thanks for any help with these questions. ARe doctors reluctant to discuss these issues because they think their patients are too stupid or because they themselves don't read?I think it is a two-fold problem. A lot of doctors don't keep up with literature-especially nowadays with the acceleration in the amount of knowledge with respect to psychopharmacology. And newer drugs coming out every month doesn't help paradoxically-it increases the number of choices complicating treatment (for a doc that is not staying on top of it).
I don't think that doctors think all their patients are too stupid. Several docs have told me they don't have the time to waste to explain how the drug is supposed to work-and if they get too involved explaining then patients may get too focused on side effects rather than their improvement as a result of the med.
poster:Mitch
thread:69089
URL: http://www.dr-bob.org/babble/20010708/msgs/69475.html