A-69024: a non-benzazepine antagonist with selectivity for the dopamine D-1 receptor

European Journal of Pharmacology
D J KerkmanJ W Kebabian

Abstract

A-69024 HBr, 1-(2-bromo-4,5-dimethoxybenzyl)-7-hydroxy-6-methoxy-2-methyl-1,2,3,4- tetrahydroisoquinoline hydrobromide, is a selective antagonist of the dopamine D-1 receptor. A-69024 HBr shows an apparent affinity toward the D-1 receptor (identified using [125I]SCH 23390) of 12.6 (4.15-38.3) nM (mean (90% CL), n = 3); the apparent affinity toward the D-2 receptor (identified using [3H]spiroperidol is 1 290 (1,200-1,380) nM (n = 3); using [125I]lysergic acid diethylamine to identify the 5-HT1C receptor gives apparent affinity of 17,800 (9,700-32,600) nM (n = 3). In assays of adenylate cyclase activity, A-69024 HBr antagonizes the D-1 receptor with a calculated affinity of 43.9 (17.5-110) nM (n = 5), while the molecule antagonizes the D-2 receptor with a calculated affinity greater than 400 nM. Behavioral studies demonstrate that A-69024 HBr (5 mg/kg s.c.) is able to block both amphetamine-induced locomotor activity and apomorphine-induced stereotypy. Furthermore, A-69024 HBr blocks SF&F 38393-, but not quinpirole-, induced rotation in rats having unilateral 6-hydroxydopamine lesions of the substantia nigra. When administered at behaviorally effective doses. A-69024 HBr neither increases the concentration of serum prolactin nor ...Continue Reading

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Citations

Jan 1, 1996·Journal of Neural Transmission·R MarksteinD Hoyer
Jun 25, 1991·European Journal of Pharmacology·M P DeNinnoL Bednarz
Aug 1, 1991·Pharmacology, Biochemistry, and Behavior·D R BrittonD Kerkman
Mar 1, 1992·Neurochemistry International·J W KebabianK E Asin
Dec 1, 1993·Schizophrenia Research·A ZaretskyX Fornazzari
Apr 4, 2002·Nuclear Medicine and Biology·Michael KassiouBernard Maziere
Nov 13, 2008·PloS One·Uri Yerushalmi, Mina Teicher
Nov 29, 2013·Journal of Labelled Compounds & Radiopharmaceuticals·Olaf PranteAshutosh Banerjee

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