How scopolamine (and such tropane alkaloids) could be modified to inhibit DA reuptake

[Nagelfar]

Might a (additionally, simply, altered) stereoisomer of scopolamine be a dopamine reuptake inhibitor? (Seeing as there are reverse isomer analogues of cocaine that are anticholinergics? i.e. difluoropine)

Actually, I'm wondering how much of an analogue besides altering stereochemistry scopolamine would have to be, to be a DRI (inhibiting dopamine release), regardless of how simple it may be.

Any insight / suggestions?

Cocaine:

Scopolamine:

 

[sekio]

The ester bridge on the tropane seems to be needed for good DAT binding, compare tropacocaine vs real cocaine

 

[Nagelfar]

Could it be that simple? (Perhaps turning this levo-wedge bond into a dextro or similar optical turn-about?)

It looks like someone removed the benzoyl group from cocaine and put an inverted substituted amphetamine in its place.

 

[Astavats]

I'm not familiar with DRI structure-activity but why are you keeping the epoxide - is this beneficial?

 

[Nagelfar]

I'm not familiar with DRI structure-activity but why are you keeping the epoxide - is this beneficial?

I'm just looking for the simplest number of steps away from scopolamine proper to be a DRI. I wouldn't know how the epoxide would affect DA inhibition, but it's certainly not necessary to it (even in this configuration, I am guessing).

 

[sekio]

I think scopolamine is a really poor lead compound for a DAT ligand, the epoxide and hydroxyl group on the phenylpropionyl group smell like bad news to me - try 4-fluoromeperidine or something maybe?