[³H]A-69024: A non-benzazepine ligand for in vitro and in vivo studies of dopamine d1 receptors

[³H]A-69024 has been prepared as a radioligand for studying the dopamine D₁ receptor. [³H]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 biodistribution of [³H]A-69024 showed a high uptake in the striatum (5.9 %ID/g) at 5 min followed by clearance. As a measure of specificity, the striatum/cerebellar ratio reached a maximum of 6.7 at 30 min post-injection. Pre-treatment with the D₁ antagonist R(+)SCH 23390 (1 mg/kg) reduced this ratio to unity. The dopamine antagonist (+)butaclamol and unlabeled A-69024 inhibited striatal uptake by 70 and 51%, respectively. Spiperone (D₂/5-HT_2A) and ketanserin (5-HT_2A/5-HT_2C) at doses of 1 mg/kg had no inhibitory effect on [³H]A-69024 uptake in the striatum; however, increased uptake of [³H]A-69024 by > 30% in the whole brain was observed. The selectivity and affinity of [³H]A-69024 suggests that this non-benzazepine radioligand may be useful for in vitro and in vivo studies of the dopamine D₁ receptor.