Selective and stereospecific interactions of R-SK & F 38393 with [3H]piflutixol but not [3H]spiperone binding to striatal D1 and D2 dopamine receptors: comparisons with SCH 23390

Abstract

Four benzazepine derivatives, racemic SK&F 38393, its resolved R- and S-enantiomers, and SCH 23390 have been investigated for their interactions with striatal D1 and D2 dopamine receptors, as indexed by the binding of [3H] piflutixol and [3H]spiperone respectively. For the agonist SK&F 38393, its R-enantiomer was active in displacing [3H] piflutixol while its S- antipode was 100 fold less potent. In contrast, both enantiomers showed similar and negligible activity to displace [3H]spiperone. SCH 23390, an antagonist analogue with an R-configuration, potently displaced [3H] piflutixol but not [3H]spiperone. R-SK&F 38393 and SCH 23390 may help clarify the structural requirements for, and functional consequences of, selective actions at the D1 dopamine receptor.