CHARACTERIZATION OF THE BINDING OF H-3-SCH 23390, A SELECTIVE D-1 RECEPTOR ANTAGONIST LIGAND, IN RAT STRIATUM

A novel benzazepine, SCH 23390 [R-(+)-8 chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol hemimaleate], was recently described as a very potent and selective dopamine D-1 receptor antagonist based on its potent inhibition of dopamine sensitive adenylate cyclase and its selective displacement of 3H-piflutixol from rat striatal receptor sites. The in vitro binding of 3H-SCH 23390 to specific striatal receptor sites was characterized. Binding was saturable and stereospecific, and the results of both saturation and competition studies are consistent with the binding of 3H-SCH 23390 to a single striatal site. A Kd of 0.53 nm was obtained through Scatchard analysis. Relative potencies of a variety of neuroleptics in competing with 3H-SCH 23390 and also 3H-spiperone support an interpretation that the single site to which 3H-SCH 23390 binds is the D-1 dopamine receptor. Also, the binding capacity of 3H-SCH 23390 (69 pmol/g wet wt) is in agreement with published values for the binding capacities of 3H-piflutixol and 3H-flupentixol. These data, coupled with the low level of nonspecific binding encountered with this radioligand (4-8% of total binding at normally employed ligand concentration of 0.3 nM), its high specific activity and its negligible binding to plastic and glass surfaces makes it ideally suited for studying interactions with this receptor.