allotropacocaine

[Nagelfar]

J Pharmacol Exp Ther. 2013 Jul; 346(1): 2–10. FIGURE ONE

^I mis-read this before, so PTs and cocaine are typical (didn't notice the A & B in figure, and saw the last listing of compounds and assumed them to be the 'atypical' kinds spoken about), but "allotropacocaine" (is this an isomer, a coca alkoid or a metabolite? Any insights?) is atypical like benztropines.

I'm curious to how it is different, when so many others are not.

 

[serotonin2A]

Allotropacocaine is an isomer of tropacocaine.

If you look over the structures, some trends are apparent. Assuming all the amines bind in the same part of the transporter, it looks like the aryl rings in the typical and atypical inhibitors bind to different regions of DAT. You can see that the aryl ring in allotropacocaine probably overlaps with one of the aryl rings in benztropine and GBR12909. By contrast, the aryl rings in cocaine and tropacocaine would interact with a different region of the transporter. Those difference probably explain why different transporter states are preferentially stabilized by the different ligand classes.

EDIT: The other interesting thing is, just by eyeballing the structures in 2D, it likes like the phenyl rings in benztropine and GBR may occupy both of the aryl-binding regions.