[Sympathomimetic enantiomers: correlation between configuration and effect on neuronal catecholamine uptake]

A mechanism responsible for the difference in the activity of enantiomers of sympathomimetics (SMs) as inhibitors of the neuronal uptake of catecholamines was studied using the SM molecular models built in preferred conformations at the binding sites. It is shown that the substituents of SM enantiomers interacting with the binding sites of membrane transporters may occupy both energetically favorable and unfavorable (configuration-dependent) positions at the asymmetric carbon atoms. Estimating the positions of these substituents, it is possible to rationalize a relationship between the configuration of SM enantiomers and the rank order of their inhibiting potency.