Posted by bleauberry on July 29, 2008, at 20:59:27
In reply to Atypical Antipsychotic Augmentation Theories?, posted by Bob on July 29, 2008, at 19:30:06
I love talking theories, even as I humbly submit to their uselessness.
Some possible things to ponder:
The AAPs do not permanently block dopamine receptors. They attach and let go frequently, allowing some dopamine to play its natural role. Very high doses are needed for all-out blockade.
The 5ht antagonism, DA antagonism, and NE antagonism all cause a release of more neurotransmitters.
Some pharmacologists theorize it is the 5ht antagonism doing the good work. It stimulates the release of all neuros, not just 5ht, and at the same time partially blocks the ones that cause mood problems.
Some of the DA receptors partially blocked are the ones sensing how much DA is present, so they will in turn send instructions to release more DA. Since the receving DA receptors are not totally blocked, some of that extra DA is getting through.
Some studies have shown that DA can be taken up into serotonin receptors, and that serotonin can be taken up into DA receptors...a possible explanation for AD sexual dysfunction. Some NE receptors also can take up DA. So as the neuros are all increased by AD+AAP, maybe some of those neuros are getting involved in crosstalk with other systems.
Anyway you look at it, many studies show that AAPs increase neuro levels in the brain, and the amount of the increases of each neuro are somehow influenced by the particular AD being used. For example, prozac+zyprexa increase all 3 neuros, above and beyond what prozac does alone. But zoloft+zyprexa increase only DA, above and beyond what zoloft does alone. Since prozac has some 5ht antagonism, that brings us back to that theory again.
Another possibility is that it all has nothing to do with neuros at all. Can't seem to find it now, but I saw an interesting study that showed how zyprexa turned up the volume on over a dozen different genes (weight gain being one), and turned down the volume on over a dozen other ones. Maybe one or several of those genes were tweeked in a way that affected mood.
Purely theories and probably totally wrong. The brain is too complicated.
poster:bleauberry
thread:842918
URL: http://www.dr-bob.org/babble/20080727/msgs/842937.html