Posted by tealady on December 13, 2004, at 17:50:52
In reply to Re: SSRI/dopamine antagonism, posted by raybakes on December 13, 2004, at 7:43:22
Hi Ray, thanks interesting article.
I found this to be an easier to read version http://www.sph.uth.tmc.edu/course/occupational_envHealth/bamick/home/TPSH%20Seminar%20Series%20Materials/Shively%20January%202004/Shively-Pharmacogenomics2003.pdf
The article seems to be saying...
* in depression, 5-HT and SERT both low (pp5)
progestins block estrogen effects..so lower TPH (pp4 TPH reduced to Ovarietomized level when progestin added)..read "low dose contraceptive pill"..so less 5-HT synthesis..leads to lower 5-HT
if estrogen( any form) up
. Tryptophan hydroxylase (TPH) up
leads to serotonin (5-HT) synthesis up
. serotonin reuptake transporter(SERT) up
. neuronal firing up(probably..seemed to be assumed)and vice-versa
sustained Low grade stess..as in lower status in the group(perhaps sustained raised cortisol levels?) leads to lowered TPH
** Also 5-HT prevents SERT degradation. (protective effect of 5-HT blocked by SSRI)
Now we have a typically depressed female with lowish estrogen levels (maybe after being on the pill, or perimenopause, menopause etc) ...given an SSRI (reuptake inhibitor) or some progestins ..or both is they are lucky!
SSRI blocks reuptake leads to
SERT lowered **
serotonin(5-HT) in synapses up
so initially feel a bit of an antidepressant effect
but 5-HT was low to start with * ..so still not enough 5-HT for enough reliefIn addition the SSRI ups DAT(previous post)..so less dopamine in synapse..so feels like its not the answer even if it has a slight effect
As well the SSRI has lowered the SERT..
also the extra 5-HT(even though not a lot) has desensitied the receptors ....hmm this IS how it works!
Guess that fits http://www.dr-bob.org/babble/alter/20031003/msgs/265672.htmlI guess you can tell I was not impressed with SSRI's, despite admiting to some slight antidepressant relief..there was something wrong with how I felt
Jan
poster:tealady
thread:428740
URL: http://www.dr-bob.org/babble/20041211/msgs/429028.html