[3H]SCH 23390 binding to human putamen D-1 dopamine receptors: stereochemical and structure-affinity relationships among 1-phenyl-1H-3-benzazepine derivatives as a guide to D-1 receptor topography.
A series of 1-phenyl-1H-3-benzazepine analogues were assessed for enantiomeric and structure-affinity relationships at human putamen D-1 dopamine receptors labelled with [3H]SCH 23390. Substitution at the 7-position of both 3-H and 3-methyl benzazepine molecules critically affected affinity for these receptors over a 500-fold range. The general rank order of potency of 7-substituents was Cl = Br much greater than CH3 greater than OH greater than or equal to H. 3-Methyl substituents increased the affinity of 7-H and 7-OH compounds two- to fivefold compared to desmethyl counterparts. The displacement of [3H]SCH 23390 binding showed substantial enantioselectivity; the R-enantiomer of SKF 83566 was 500-fold more potent that its S-antipode. However, the displacement of [3H]spiperone binding from D-2 sites in the same tissue showed negligible enantioselectivity. Through such structure-affinity relationships, these studies may help to define the topography of the human brain D-1 dopamine receptor and guide the design of more selective agents for functional studies.
D000368:Aged; D001552:Benzazepines / Q000378:metabolism*; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008968:Molecular Conformation; D011699:Putamen / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D013134:Spiperone / Q000378:metabolism; D013329:Structure-Activity Relationship
D001552:Benzazepines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D013134:Spiperone