[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 KD = 14.3 +/- 3.2 nM (mean +/- SEM; n = 3) and Bmax = 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-HT2A) and ketanserin (5-HT2A/5-HT2C) 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.
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D018492:Dopamine Antagonists / Q000378:metabolism*; D008297:Male; D051379:Mice; D010208:Papaverine / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D044005:Tetrahydroisoquinolines
D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D044005:Tetrahydroisoquinolines; C061450:A 69024; D010208:Papaverine