on http://pdsp.med.unc.edu/pdsp.php it looks like ki value is lower for the sert than for 5htc. so i don't think this would work.
Anyone can explain how to use this? Thanks.
Sure. Pick the compound you're investigating from the "Test Ligand" drop-down box. It doesn't seem to work when typed into the text box; I'm not sure why.
It helps weed out undesirable results if you also select "Human" from the Species drop-down, and since both SERT and 5HT2C are part of the serotonin system, you can pick 3H-5HT from the "Hot Ligand" drop-down. This isn't necessary, but it helps make your results easier to interpret.
As it turns out, fluoxetine's Ki for human SERT is, on average, several orders of magnitude lower than that for 5HT2C when tested in its ability to displace Tritium-labelled serotonin (which is what 3H-5HT means) from either receptor. Thus, you will already have significant SERT inhibition before you even begin to get relevant amounts of 5HT2C antagonism.
Sad, because I too would love to find a selective 5HT2C inhibitor! I have ADHD, and 5HT2C antagonism (hell, even partial agonism) could be a godsend. It would increase dopamine and norepinephrine release, and also reduce worry. While people with ADHD probably only have minor biological predispositions to worry, there are major psychological reasons a person with ADHD would develop anxiety.
Then again, I shouldn't complain. We ADHDers often have sleep difficulties, and agomelatine would help greatly with that. I'd love to try it some day. How are you liking it?
I'm not quite sure why you'd want MAO-B selective selegiline. Presumably for depression? In general, studies consistently fail to demonstrate even minor antidepressant effects of MAO-B selective doses. You need MAO-A inhibition to treat MDD or dysthymia. Perhaps you're wanting to augment the dopamine release from the agomelatine? That would probably increase euphoria and attention span. But in order to reverse the reward-dependance failure so typical of depression, you'll need to target the norepinephrine system, not the dopamine system. A better combo might be agomelatine + low-dose bupropion or agomelatine + yohimbine. Either of those augmentation strategies would target the norepinephrine system more effectively, and unlike low-dose selegiline, they are proven to enhance the actions of other antidepressants.
BTW, why do you want to avoid SERT inhibition? If you did use an SRI, it would probably enhance the action of agomelatine. It would increase the rate at which your 5HT2C receptor would down-regulate (thank god those things already down-regulate in response to antagonists), and the pre-existing antagonism of the 5HT2C receptor should prevent many of the side effects, including sexual side effects and anxiety.
Summary of these suggestions: Combine agomelatine with yohimbine, bupropion, or fluoxetine. Each of these augmentation strategies has a likely mechanism for success in treating MDD, unlike adding low-dose selegiline. But if you added high-dose selegiline, that would almost certainly work too!
