Characterization of the binding of /sup 3/H-SCH 23390, a selective D-1 receptor antagonist ligand, in rat striatum

Journal Article · Mon Oct 29 00:00:00 EST 1984 · Life Sci.; (United States)

DOI:https://doi.org/10.1016/0024-3205(84)90540-X· OSTI ID:6241826

Billard, W; Ruperto, V; Crosby, G; Iorio, L C; Barnett, A

A novel benzazepine, SCH 23390, has recently been 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 /sup 3/H-piflutixol from rat striatal receptor sites. In the present study, the in vitro binding of /sup 3/H-SCH 23390 to specific striatal receptor sites has been characterized. Binding was saturable and stereospecific, and the results of both saturation and competition studies are consistent with the binding of /sup 3/H-SCH 23390 to a single striatal site. A K/sub D/ of 0.53 nM was obtained through Scatchard analysis. Relative potencies of a variety of neuroleptics in competing with /sup 3/H-SCH 23390 and also /sup 3/H-spiperone support an interpretation that the single site to which /sup 3/H-SCH 23390 binds is the D-1 dopamine receptor. Also, the binding capacity of /sup 3/H-SCH 23390 (69 pmoles/gm wet weight) is in agreement with published values for the binding capacities of /sup 3/H-piflutixol and /sup 3/H-flupentixol. These data, coupled with the low level of non-specific binding encountered with this radioligand (4-8% ot total binding at normally employed ligand concentration of 0.3 nM), its high specific activity and its negligible binding to plastic and glass surface make it ideally suited for studying interactions with this receptor.

• Research Organization: Schering-Plough Corp., Bloomfield, NJ
• OSTI ID: 6241826
• Journal Information: Life Sci.; (United States), Vol. 35:18
• Country of Publication: United States
• Language: English

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550201* - Biochemistry- Tracer Techniques