Posted by PeterJ on May 17, 2000, at 23:05:42
In reply to Re: SSRIs: - Different, posted by Cam W. on May 17, 2000, at 19:21:46
>
> Peter - The reason why SSRIs are act differently in different people is that they attach to receptors other than serotonin. Everyone has a different body make up and will react differently to SSRI attachment. This is partially what causes the different effects (eg anti-anxiety effect with Paxil). What the SSRIs all have in common is that they bind (and block) to the serotonin reuptake site on the presynaptic neuron. Although they are called "Selective" Serotonin Reuptake Inhibitors (SSRI), they do not bind 'only' to serotonin reuptake receptors (with the possible exception of Celexa).Thanks, Cam.
I was aware of the differences in binding to non-serotonergic sites. In fact that's the reason I'm trying Celexa, as it is the "purest" SSRI.
The thing is, if you look at the IC50 or Ki values for the SSRIs at various receptors, there is, in most cases, a 10 to 1000-fold separation in the concentrations needed to block serotonin uptake versus that needed to affect other receptors. For example Zoloft is about 16 times more potent at blocking serotonin uptake than at blocking dopamine uptake. One could take a dose of Zoloft that saturates serotonin uptake and still have mimimal effect on dopamine uptake, if--and it's a big "if"--in vivo and in vitro values correlate.
If you go by the binding values one might expect the differences between SSRIs to be fairly subtle. They are all primarilly SSRIs with some other mild affects. But some people do report pretty dramatic effects between SSRIs.
Differences in metabolism probably account for some of it. And perhaps the slight differences in receptor binding make more difference than one might expect on purely quantitative grounds.
Drug company reps tend to emphasize the differences to differentiate their own products. But many doctors are sceptical of the reality of these differences.
What I am trying to get a handle on is how different these drugs are clinically. If you had 100 people on Prozac and switched them all to Celexa or to Paxil, how many could tell the difference? Would some notice a big difference?
Or to put it another way, if you have tried one or two or three SSRIs can you conclude that you know how you respond to SSRIs in general or are they different enough that you would want to try them all. If you did not respond to some of them, might you respond to others.
There has been some work on this question, but not much. I appreciate your comments and those of the other babblers who have posted in this thread. All the comments have been helpful and I encourage others to respond with their SSRI experiences.
Peter
poster:PeterJ
thread:33808
URL: http://www.dr-bob.org/babble/20000517/msgs/33845.html