Posted by Mitch on July 8, 2001, at 16:45:45
In reply to Re: Going Crazy: Could it be Buspar????? » Mitch, posted by Elizabeth on July 8, 2001, at 15:35:57
Elizabeth-trust me I wasn't speculating about mechanisms when I stopped it! It was after I stopped it and the hostility subsided that I began to speculate-because I liked the effect it had of nearly completely eliminating almost all of my anxiety-that is a mind-blowing feat in itself-that is what got my curiousity about mechanisms. I was taking 5mg/day for about two weeks-felt much lowered anxiety, but I was starting to gripe and complain about stuff at work more often. Then I boosted it to 10mg/day for about another week, that was when the hostility kicked in. I would get so angry my heart would just race and race, and I would be thinking all sorts of hostile stuff "That asshole is going to get some payback you'll see!"-and worse than that. I slept ok-I wasn't euphoric or agitated (not classicly hypomanic). It was like I LIKED BEING PISSED OFF-so it wasn't any kind of miserable dysphoria in that sense.
I am not that interested in *how Buspar works* so much as *why did I get so hostile when I took it*.
When I mentioned the *lowered serotoinin* I was referring to what the patient sample package described. It said that excessive anxiety could be due to an excess of serotonin and that Buspar worked to reduce excessive serotonin-or something to that effect. Then when I was checking out the drug itself I came across this medline abstract-that made it appear that extracellular serotonin was being cut, while extracellular DA and NE was getting boosted. The extracellular DA is probably what caused my hostility, but not sure.
Anyhow, here goes;Neuroscience 1999;93(4):1251-62
Buspirone modulates basal and fluoxetine-stimulated dialysate levels of dopamine, noradrenaline and serotonin in the frontal cortex of freely moving rats: activation of serotonin1A receptors and blockade of alpha2-adrenergic receptors underlie its actions.
Gobert A, Rivet JM, Cistarelli L, Melon C, Millan MJ.
Institut de Recherches Servier, Psychopharmacology Department, Croissy-sur-Seine, Paris, France.
The serotonin1A receptor partial agonist, buspirone, also displays antagonist properties at D2 receptors and is metabolized to the alpha2-adrenergic receptor antagonist, 1-(2-pyrimidinyl-piperazine). Herein, we examined mechanisms underlying the influence of buspirone alone, and in association with the serotonin reuptake inhibitor, fluoxetine, upon extracellular levels of serotonin, dopamine and noradrenaline simultaneously quantified in the frontal cortex of freely moving rats. 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%). 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. In contrast to buspirone, the serotonin reuptake inhibitor, fluoxetine (10.0), increased frontocortical levels of serotonin (+ 120%), dopamine (+55%) and noradrenaline (+90%). 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 serotonin1A agonist, 8-hydroxy-2-(di-n-propyl-amino)-tetralin (0.16), mimicked the action of buspirone in reducing resting levels of serotonin (-60%) and in enhancing those of dopamine (+135%) and noradrenaline (+165%). Like buspirone, it attenuated the influence of fluoxetine upon serotonin levels, yet facilitated its influence upon dopamine and noradrenaline levels. In contrast, WAY 100,635 selectively potentiated the increase in levels of serotonin (two-fold) versus dopamine and noradrenaline elicited by fluoxetine. Further, WAY 100,635 abolished the inhibitory influence of buspirone upon fluoxetine-induced serotonin release, but only partly interfered with its potentiation of fluoxetine-induced increases in dopamine and noradrenaline levels. The D2/D3 receptor antagonist, raclopride (0.16), increased basal dopamine (+60%) levels but little influenced those of serotonin and noradrenaline, and failed to modify the action of fluoxetine. The alpha2-adrenergic receptor antagonist, 1-(2-pyrimidinyl-piperazine) (2.5), which did not modify resting levels of serotonin, markedly increased those of dopamine (+90%) and noradrenaline (+190%) and potentiated (two-fold) the increases in dialysate levels of dopamine, noradrenaline and serotonin provoked by fluoxetine. Further, the alpha2-adrenergic receptor agonist, S18616, attenuated the enhancement by buspirone of the fluoxetine-induced increase in levels of dopamine and noradrenaline. 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. However, its principal mechanism of action in this respect is probably the alpha2-adrenergic antagonist properties of its metabolite, 1-(2-pyrimidinyl-piperazine). The present observations are of significance to experimental and clinical studies of the influence of buspirone upon depressive states, alone and in association with antidepressant agents.
PMID: 10501449 [PubMed - indexed for MEDLINE]
> If it was making your temper or mood worse to a point where you couldn't function, then it probably was best to go off it (without any need to speculate about the mechanism whereby it did this). What dose were you taking, and for how long?
>
> -elizabeth
poster:Mitch
thread:69089
URL: http://www.dr-bob.org/babble/20010708/msgs/69418.html