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[ 3 H]SCH 23390 Binding to Human Putamen D‐1 Dopamine Receptors: Stereochemical and Structure‐Affinity Relationships Among l‐Phenyl‐1 H ‐3‐Benzazepine Derivatives as a Guide to D‐l Receptor Topography
Author(s) -
O'Boyle Kathy M.,
Waddington John L.
Publication year - 1987
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1987.tb05623.x
Subject(s) - benzazepine , sch 23390 , chemistry , desmethyl , enantiomer , stereochemistry , d 1 , receptor , dopamine receptor , dopamine , spiperone , biochemistry , biology , endocrinology , metabolite
A series of l‐phenyl‐1 H ‐3‐benzazepine analogues were assessed for enantiomeric and structure‐affinity relationships at human putamen D‐1 dopamine receptors labelled with [ 3 H]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 ≫ CH 3 > OH ≥ H. 3‐Methyl substituents increased the affinity of 7‐H and 7‐OH compounds two‐ to fivefold compared to desmethyl counterparts. The displacement of [ 3 H]SCH 23390 binding showed substantial enantioselec‐tivity; the R‐enantiomer of SKF 83566 was 500‐fold more potent that its S‐antipode. However, the displacement of [ 3 H]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 selecive agents for functional studies.