Characterization of binding of 3H-SCH 23390 to dopamine D-1 receptors. Correlation to other D-1 and D-2 measures and effect of selective lesions

The binding of 3H-SCH 23390 to membranes from rat and mouse brain tissue has been investigated. The binding was saturable and reached equilibrium after 60 minutes. Nonspecific binding was low. Association and dissociation rates were Mg++-sensitive. In almost all respects the binding of 3H-SCH 23390 was comparable to the binding of 3H-piflutixol and 3H-cis(Z)-flupentixol. The density of binding sites in striatum was greater than in limbic structures which in turn was greater than in frontal cortex. The density of binding sites in these structures were comparable with those of 3H-piflutixol and 3H-cis(Z)-flupenthixol, 2-3 times higher than the D-2-receptor density. Whereas an increase was seen in 3H-SCH 23390 binding. The binding was decreased approximately 72% 3 weeks after unilateral kainic acid lesion whereas that of 3H-spiperone was only decreased 56%. Finally, the affinities of neuroleptics to the 3H-SCH 23390-binding sites correlated to the affinities to 3H-piflutixol-binding sites and to the effects on DA-sensitive Adenylate Cyclase. Agonist competition curves were shallow and the data best fit a two-site model composed of a high and a low affinity component. Thus, 3H-SCH 23390 is regarded as a highly selective ligand for brain dopamine D-1 receptors in vitro.