SSRI structural similarities?

[Chromic]

I've taken a moment of time and drawn out the structural diagrams for the tricyclics. They all look very, very similar to me.

Then I took a moment to draw out the SSRIs, Prozac, Luvox, Celexa, Zoloft and Paxil. Now, I'm very confused.

What is the reason that all these chemicals go through the serotonin reuptake channel?

I see that they all have electron withdrawing substituents on a phenyl ring. Either a 3,4- chloro on zoloft, a 4-fluoro on Paxil and Celexa or a 4-trifluoro on Luvox and Prozac. Is this the reason? And is the reason they inhibit serotonin reuptake because they bind to the reuptake channel but because of the large subsituents they can't pass through it?

Could one take safrole and make an antidepressant of it by branching a big long chain ending in a secondary amine?    I'm probably sounding like fman to more knowledgeable bees, but I'm just shooting in the dark trying to make sense of a trend I can't quite discern?

[GlaseIs]

I have also looked the the structures.. the thing that interested me was that Paxil has the 1,3-benzodioxole structure integrated into it. Unfortunately its an ether linkage. Hehe not like anyone would buy Paxil to make MDMA at the price Paxil runs. The 1,3-benzodioxale has to have something to do with the serotonin receptors. The only thing I can think of is that all the other junk on the molecule just makes it harder to work like it should (like MDMA )
On the 6th day God created man. On the 7th day, man returned the favor.

[Chromic]

Well, MDMA enters the axons via the reuptake channels. If they're inhabited by SSRIs, the effects of MDMA are diminished as it's harder for the MDMA to get in to do it's dirty work on the vesicles (? just my theory ?) It looks like electronegative aromatics get pumped through by this protein complex. It's not surprising information when one looks at the structure of serotonin itself.

Fuck, I wish I had the DNA sequence for the pump along with some really good chemistry modelling software... This stuff looks so (freaking) interesting to me!

I wonder if the methylenedioxy bridge is the active part on Paxil, and because ring hydroxylation occurs easily with MDMA maybe it does occur easily on Paxil contributing to its relatively short half-life. (note I found out that Paxil is metabolized by CYP2D6, but I can't find out what CYP2D6 actually does! -- this sort of borders with my other thread on cytochrome P450... I also found that oxidation and methylation is the form of metabolism, but can't find the specific metabolites, unlike MDMA... where it's easy to find out what it's metabolized to)

Arrgh. I have "some" information to conjecture just "not enough" to get any answers...

[PoohBearium]

I doubt this will help, but I feel almost as if I were rolling just with the prescribed 20mg dosage; I prefer 1/2 dose just to take the edge off when I need to accomplish something.

PB

BTW, what do you consider a short half life?  I know it takes 20 days to build up in your system, but it feels like several days before the effects are completely gone...  
Put your left leg down - your right leg up,
Tilt your head back - let's finish the cup!

[Chromic]

Paxil and Zoloft both have short half-lives, ~20hrs and ~24hrs respectively. Prozac has a long-half life, IIRC, ~7 days.