Affinity for dopamine D-2, D-3, and D-4 receptors of 2-aminotetralins. Relevance of D-2 agonist binding for determination of receptor subtype selectivity

A series of 2-aminotetralins, substituted with a methoxy or a hydroxy group on the 5- or 7-position, and with varying N-alkyl or N-arylalkyl substituents, were prepared and evaluated in binding assays for human dopamine (DA) D-2, D-3, and D-4 receptors. Some members of this series were prepared in former studies, but were never tested in vitro with single receptor subtypes, and these were examined again. None of the tested 2-aminotetralins showed high affinity for the dopamine D-4 receptor. However, a number of the 2-aminotetralins showed high affinity for both the D-2 and the D-3 DA receptors, as exemplified by compounds 11-15 and 21-26, while some had a reasonable selectivity for the DA D-3 receptors. The affinities of the 2-aminotetralins for the D-2L receptor depended on the type of radioligand (agonist or antagonist) used. The agonist affinity data, obtained by using the agonist ligand [H-3]N-0437, are thought to be more relevant for calculating DA receptor subtype selectivity.