Posted by cache-monkey on April 26, 2005, at 1:16:18
In reply to Re: Effects of Selegiline's amphetamine metabolite » cache-monkey, posted by chemist on April 25, 2005, at 20:31:02
<< hello there, chemist here...please pardon my jumping in on your thread >>
Hi Chemist,
Wouldn't say you were jumping in. Up thread a ways (where I was asking about selegiline) I waved a flag for you!I'm not a pharmacologist, or a chemist for that matter. I'm just starting to get a basic understanding of how the balance between various drugs and their metabolites are going to affect me. (I have to be a little more careful than most since I am an "intermediate" -- a lot closer to "poor" than "extensive" -- CYP-2D6 metabolizer.)
So, unfortunately the rest of your post is a bit above my head. Sorry I can't be of more help!
Best,
cache-monkey
...the question i have in mind is what you address in noting the selectivity for the diastereomeric pairs (ref [3])...the IC50 values for the (2S,3S) and (2S,3R) HB metabolites in the mol. pharm. article are striking, yet mimic what we see with alpha4beta2 and alpha7 nAChR specificity for nicotine and derivatives (they ``like'' (S)). given the stereospecificity of (excuse my lapse in enzymology here and elsewhere!) almost all enzymes we have categorized, is it likely that your HB diastereomers are ``victims'' of induced fit for the 2D6 after the tert-butyl group is removed? this does leave a nitrogen that is attractive to 2D6, while the bulk of the t-butyl is absent...assuming the beta-hydroxylation is followed by a leaving t-butyl and demethylation, we are looking at something darned close to epi...your thoughts and guidance requested, if you please, as i ought to be set straight and am in the dark at the moment.....thanks much, and all the best, chemist
poster:cache-monkey
thread:487473
URL: http://www.dr-bob.org/babble/20050423/msgs/489643.html