Posted by conundrum on February 23, 2010, at 13:56:46
In reply to Re: D2 And 5HT2A: Dopamine Blocking And Boosting, posted by Brainbeard on February 23, 2010, at 9:07:11
>Yeah, but don't forget Prozac is a more potent 5HT2C-antagonist.
That would seem to be so, since its more activating and the least sleep promoting of the SSRIs. The Lilly study I posted showed that Prozac has a similar potency for both types of 5-HT2 receptors. 119 ± 10 for 2A and 118 ± 11 for 2C. Its interesting that no other studies even mention the 5 HT2A antagonism. Is this just something else that Lilly cooked up like when they hid suicidal ideation caused by the drug or the metabolic problems with Zyprexa?
Also, The study linked below uses Ki 5 and not just Ki, I guess this is the same potency but just at a different scale or is the data just different? In the PNAS article the Ki is much weaker at the 5 HT pump than the Lilly study and stronger as a 5 HT2C antagonist.
http://www.pnas.org/content/94/5/2036.full.pdf>No, 5HT2A/C receptors downregulate throught the SSRI's indirect agonism also. It's strange, downregulation of 5HT2C-receptors at least would mediate enhanced dopaminergic functioning, as well as weight gain, but with SSRI's our picture isn't exactly one of enhanced dopaminergic functioning, althoug the weight gain does show up usually to be sure. Personally, SSRI's stimulate pleasure seeking behavior in me and tend to make me hypersexual MENTALLY, which may be symptoms of 5HT2C downregulation.
Even though downregulation occurs with SSRIs I imagine only an antagonist would significantly increase DA/NE release. After all you are still activating those downregulated receptors with an SSRI even if there are less of them and they are desensitized. Did you notice any difference between prozac and other SSRIs? I've noticed the lexapro makes everything limp and not just between my legs. It makes me tired and slows my thinking down. Prozac is kinda similar at higher doses. I've noticed an increase in motivation and possibily hedonia after about month of taking 5mg every other day. I wonder how low I can go and still get an effect? Did you notice any activating effects of prozac immediately? I don't. It seems that 5 HT receptors need about a month to become downregulated in order to increase NE/DA OR that NE/DA are increased immediately and that those systems need to adapt. Then there is the whole waiting 29 days to reach a steady state problem.
If what I really need is NE this is a hell of a way to get it. A tricyclic might be a better route.
One of the main problems with these studies is some seem to say at a higher dose NE/DA is boosted, like if you look at the Lilly study where they found 3mg/kg didn't have much of an effect but 30mg/kg had increase NE more than SER However the one you posted here seems to say the opposite:
http://www.pnas.org/content/94/5/2036.full.pdfAlso how do these doses compare to humans? 3 mg/kg seems like a lot if you ask me, but rats metabolize quickly.
Do you have any resources for explaining IC 50 and Ki and all that stuff?
>Yeah, and how about combining hypotheses based on science with thorough experimentation? That's what I try to do, though not all of my doctors appreciate it as much.. ;)
Pdoc said I have an obsessive disorder for trying to solve this problem scientifically, not an affective disorder. He said its like throwing darts on a board and seeing what works. I just don't want to waste my time taking drugs that may not work or could have horrible withdrawals. So far the only dart that has had any benefit was low dose prozac with buspar, and thats something that I thought out here thanks to your posts.
poster:conundrum
thread:907193
URL: http://www.dr-bob.org/babble/neuro/20100223/msgs/937752.html