The chemical basis for the blockade of the D-1 dopamine receptor by SCH 23390

SCH 23390 (R(+)-7-chloro-8-hydroxy-2,3,4,5-tetrahydro-3-methyl-1-phenyl-1H-3 -benzazepine) is a potent, relatively selective antagonist of the D-1 dopamine receptor ( Iorio et al., J. Pharmacol. Exp. Ther. 226, 462). Because SKF 75670, the 7-OH analogue of SCH 23390, is a partial D-1 agonist, we conclude that the 7-Cl substituent of SCH 23390 contributes to its D-1 antagonist activity. Because SKF 83509, the desmethyl analogue of SCH 23390, is a selective D-1 antagonist, we conclude that the N-methyl substituent of SCH 23390 is not essential for its D-1 antagonist activity.