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

Michael Kassiou, Ursula A. Scheffel, John L. Musachio, Marigo Stathis, Robert F. Dannals

Research output: Contribution to journalArticle

Abstract

[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.

Original languageEnglish (US)
Pages (from-to)PL367-PL372
JournalLife Sciences
Volume57
Issue number23
DOIs
StatePublished - Oct 27 1995

    Fingerprint

Keywords

  • dopamine D receptor
  • radioligand
  • tritium

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this