Steven and others…
I have been considering switching from Sertraline to Prozac. I would appreciate your thoughts:
Heres what I know based on what Steven has written on his web site.
- When sertraline was added to doxorubicin it resulted in increased chemosensitive over fluoxetine and doxorubicin. This is apparently due to sertraline’s ability to impact efflux pumps better than fluoxetine. I do not know if TMZ and doxorubicin are comparable with regards to benefits brought about by inhibiting efflux pumps.
- Prozac inhibits MGMT activity, sertraline does not
- Disulfiram inhibits MGMT activity
Then from CUSP9*:
- Sertraline blocks multiple survival pathways. No mention of this is made with fluoxetine
So here are my questions:
- If sertraline inhibits efflux pumps as does disulfiram, how important are PPI’s likely to be if both sertraline and disulfiram are already being utilized?
- Since disulfiram already inhibits MGMT activity, in theory fluoxetine would not need to be used for this (ignoring the possibility of synergy for now). And since both sertraline and fluoxetine inhibit efflux pumps, it seems sertraline might be better combined with disulfiram rather than fluoxetine and disulfiram because sertraline has the added benefit of blocking multiple survival pathways. Do you agree with my thinking on this?
- Fluoxetine does inhibit MGMT as does disulfiram and I suspect the synergy between the two could be beneficial, but since we are dealing with an IDH1 mutation, presumably most of the cells are MGMT methylated. There would of course be other cells that are not methylated that could benefit from MGMT inhibition, but with disulfiram in the mix already, do I need to prioritize fluoxetine over sertraline because of this? Or would the added benefit of blocking survival pathways be of more importance? I realize there is no known answer to this and I am asking you to offer input lacking any data, but I am wondering if based on what you have read, this makes sense.
- Jeremy is not willing to add a PDE5 inhibitor to his cocktail. I think he has had his fill of drugs and supplements. Does sertraline seem to improve BBB penetration?
Thanks for the input!