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

LIFE SCIENCES

卷:57

Letter

KASSIOU, M ; SCHEFFEL, UA ; MUSACHIO, JL ; STATHIS, M ; DANNALS, RF

关键词: DOPAMINE D-1 RECEPTOR;    RADIOLIGAND;    TRITIUM;   

DOI  :  10.1016/0024-3205(95)02212-2

来源: Elsevier

【 摘 要 】

[H-3]A-69024 has been prepared as a radioligand for studying the dopamine 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 biodistribution 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, the striatum/cerebellar ratio reached a maximum of 6.7 at 30 min post-injection. Pre-treatment with the D-1 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 (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 striatum; however, increased uptake of [H-3]A-69024 by > 30% in the whole brain was observed. The selectivity and affinity of [H-3]A-69024 suggests that this non-benzazepine radioligand may be useful for in vitro and in vivo studies of the dopamine D-1 receptor.

【 授权许可】

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