[H-3] A-69024 - A NON-BENZAZEPINE LIGAND FOR IN-VITRO AND IN-VIVO STUDIES OF DOPAMINE D1 RECEPTORS

[H-3]A-69024 has been prepared as a radioligand for studying the dopam ine D-1 receptor. [H-3]A-69024 binds to rat striatal membranes with a K-D = 14.3 +/- 3.2 nM (mean +/- SEM; n = 3) and B-max = 63.5 +/- 12.8 fmol/mg wet tissue (1.8 +/- 0.3 pmol/mg protein). This ligand binds to only one site with a Hill coefficient close to unity. The in vivo bio distribution of [H-3]A-69024 showed a high uptake in the striatum (5.9 %ID/g) at 5 min followed by clearance. As a measure of specificity, th e striatum/cerebellar ratio reached a maximum of 6.7 at 30 min post-in jection. Pre-treatment with the D-1 antagonist R(+)SCH 23390 (1 mg/kg) reduced this ratio to unity. The dopamine antagonist (+)butaclamol an d unlabeled A-69024 inhibited striatal uptake by 70 and 51%, respectiv ely. Spiperone (D-2/5-HT2A) and ketanserin (5-HT2A/5-HT2C) at doses of 1 mg/kg had no inhibitory effect on [H-3]A-69024 uptake in the striat um; however, increased uptake of [H-3]A-69024 by > 30% in the whole br ain was observed. The selectivity and affinity of [H-3]A-69024 suggest s that this non-benzazepine radioligand may be useful for in vitro and in vivo studies of the dopamine D-1 receptor.