CHARACTERIZATION OF THE BINDING OF SCH-39166 TO THE 5 CLONED DOPAMINE-RECEPTOR SUBTYPES

Characterization studies were conducted on the five cloned dopamine receptor subtypes (D-1-D-5) using the novel D-1-selective antagonist, SCH 39166, as well as other related benzazepines and dopaminergic agents. The results demonstrate that SCH 39166 exhibits saturable, high-affinity binding to the D-1 and D-5 receptors, but binds with low affinity to the D-2, D-3, and D-4 receptors. In contrast, the D-2 antagonist haloperidol showed low affinity for the ''D-1-like'' receptors and high affinity for the ''D-2-like'' receptors. A series of agonists was also evaluated and the D-5 receptor subtype displayed a two-site fit for the endogenous agonist dopamine, as well as for the agonist apomorphine. Differences in agonist binding among the D-1-like receptors reflect the importance of the nonconserved amino acid substitutions.