ELECTROSTATIC MEDIUM EFFECTS AND FORMAL QUANTUM STRUCTURE-ACTIVITY-RELATIONSHIPS IN APOMORPHINES INTERACTING WITH D-1 AND D-2 DOPAMINE-RECEPTORS

The binding of apomorphines (AM) to D-1 and D-2 dopamine receptors is analyzed through a formal quantum structure-activity relationship meth od. The calculations were carried out at the CNDO/2 level of the molec ular orbital theory with a continuum representation of environmental e ffects. The results show that the D-1 receptor affinity variation is r elated to the variation of the electron-donating capacity of a C atom of the hydroxylic region of apomorphines in a low-polarity medium. The N-chain probably interacts with a hydrophobic region of the receptor. It is also concluded that the poor results for the D-2 binding affini ty are explained by errors in the experimental measurements. Finally, it is proposed that future structure-activity relationship studies mus t be carried out for media of different polarities. (C) 1997 John Wile y & Sons, Inc.