Posted by linkadge on January 11, 2007, at 16:04:08
In reply to Re: pergolide, cabergoline: heart pathology via 5-, posted by SLS on January 11, 2007, at 1:08:47
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?
YES!! (see)
Deficiency of the 5-Hydroxytryptamine Transporter Gene Leads to Cardiac Fibrosis and Valvulopathy in Mice.
http://circ.ahajournals.org/cgi/content/abstract/113/1/81
>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.
Thats exactly it. When you start a drug and you develop a problem soon after, it is easy to implicate that drug. If you develop heart problems 20 years after starting an SSRI, nobody would suspect it.
>This is not true. That's like saying >methylphenidate is the same as bromocriptine.No, but they will shart a common ability to agonise certain dopamine receptors.
>With reuptake inhibitors, my guess is that re->regulation helps to prevent overstimulation of >receptors.
But, that reregulation occurs with agonists as well. Ie, buspar downregulates 5-ht1a. So if cardiac receptors were protected by downregulation in the presense of uptake inhibitors, then they should be protected by downregulation in the presence of agonists, which they don't seem to be.
>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.Ritalin is sometimes used for parkinsons, sometimes end stage parkinsons. I think it is not a first line treatment for the same reason it isn't a first line treatment for depression.
One would need to asess comparable doses of 5-ht agonists with uptake inhibitors.
>That's what we are talking about here with >regard to 5-HT2b receptors.
Yeah, I know. But you could have a cardiac event related to this that might not be directly seen as linked to SSRI use for that matter.
>I'd like to see the study, anyway. Were the >control subjects people who were depressed who >didn't take SSRIs?No, but depression was factored into calculations.
Not entirely conclusive, I realize.http://www.news-medical.net/?id=16395
There are also links to maternal use of SSRI's, and development of congenital heart problems to child.
> 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.
There has been a lot about supressed information related to drugs. I wouldn't put it past people to keep potential problems supressed.
Serotonin causes proliferation in a variety of human tissues.
>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.
If you mess with the serotonin transporter, you mess with serotonin throughout the body. Ie that is why some people can develop severe GI problems from SSRI use. If there is a serotonin abnormality in depression, I think it is brain specific, and that it could be fixed without altering MAO, or SERT.
Linkadge
poster:linkadge
thread:720797
URL: http://www.dr-bob.org/babble/20070107/msgs/721412.html