Posted by SLS on January 11, 2007, at 1:08:47
In reply to Re: pergolide, cabergoline: heart pathology via 5-, posted by linkadge on January 10, 2007, at 8:15:18
> > On the other bright side, it may be that direct receptor agonism is necessary for the valvulopathy, and not an effect secondary to reuptake inhibition or release. I was impressed by the fact that fenfluramine had a metabolite that was a direct agonist.
> Thats what I am afraid of. I don't think that this exonerates serotonin reuptake inhibitors from causing such problems.Perhaps not, but nor does it exonerate eating crayfish. It's just never been seen. I understand your concerns, though. Note, however, that valvulopathy has developed very quickly with 5-HT2b receptor agonists, and to my knowledge, has yet to be demonstrated with SSRIs after 20 years of usage.
> SSRI's are 5-ht2b receptor agonists plain and simple.
This is not true. That's like saying methylphenidate is the same as bromocriptine. With reuptake inhibitors, my guess is that re-regulation helps to prevent overstimulation of receptors. With a high-affinity direct receptor agonist, however, even with downregulation, occupancy remains high. If the two drugs were the same, Ritalin, a DA reuptake inhibitor, would work as well as DA agonists for Parkinsons. It doesn't.
> There was one recend study that suggested that cardiac patients who used SSRI's were more likely to die of their disease.
Valvulopathy?
That's what we are talking about here with regard to 5-HT2b receptors.
I'd like to see the study, anyway. Were the control subjects people who were depressed who didn't take SSRIs?
> I think what they are "trying" to do is establish that SSRI's don't cause a problem and that 5-ht2b agonists do. They obviously "want" to do that because direct 5-ht2b agonists are much less plentiful than SSRI's.
I wouldn't presume to read the minds of so many scientists who are in agreement about this, but I question your explanation.
> Remember that study I just posted which showed that mice who were low in the serotonin transporter developed similar cardiac problems later in life.Valvulopathy?
I tend to agree with you that dysregulation of neural tone, perhaps autoreceptor-mediated, is a more likely explanation for affective disorders than is a defect in transporter expression.
- Scott
poster:SLS
thread:720797
URL: http://www.dr-bob.org/babble/20070107/msgs/721253.html