Synthesis and dopamine receptor binding of exo- and endo-2-amino-6,7-dihydroxybenzonorbornene, rigid analogues of 2-amino-6,7-dihydroxytetrahydronaphthalene.

Two bridged tricyclic analogues of 2-amino-6,7-dihydroxytetrahydronaphthalene (ADTN) in which the amino group is held rigidly in an equatorial and axial conformation, respectively, and in which the catechol ring is twisted out of the plane of the ethylamine chain have been synthesized and assayed for their effects on the binding of [3H]dopamine, [3H]apomorphine, and [3H]spiperone to calf and rat striatal homogenates. Up to concentrations of 2000 nM, these exo- and endo-2-amino-6,7-dihydroxybenzonorbornenes displayed no ability to displace any of the radioligands from their receptor sites in the calf and rat brain homogenates, in contrast to measured IC50 values of 6 and 3.1 nM for racemic ADTN vs. [3H]dopamine in the two preparations, respectively. The enantiomers of the exo amine showed no specific activity vs. [3H]dopamine in the two preparations, respectively. The enantiomers of the exo amine showed no specific activity vs [3H]dopamine. Although negative, these data are informative in molecular modeling of dopaminergic receptor interactions.