MOLECULAR ELECTROSTATIC POTENTIAL OF D1 AND D2 DOPAMINE AGONISTS

The molecular electrostatic potential (MEP) of four selective D1, four nonselective D1/D2, and three selective D2 agonists has been calculated in a three-dimensional grid surrounding the molecules. The local density functional program DMol was used to evaluate the MEP. A comparison of the MEPs of all compounds revealed that while the electrostatic effects may be important for the affinity in both D1- and D2-selective ligands, it only appears to be a subtle modulator of the selectivity. Slight differences were found in the negative regions in the vicinity of the catechol ring that can account for the D1 versus D2 selectivity in the compounds studied.