Stereospecific blockage of the alpha adrenergic receptor by substituted 1-aminotetralines.

Certain members of a series of 1-aminotetraline derivatives reversed the epinephrine pressor response in dogs; this effect occurred with the R- but not the S-isomers. Studies with rabbit aortic strips indicated competitive blockade of the alpha adrenergic receptor by the active agents. Receptor protection experiments supported the interpretation that this disruption of receptor function was due to occupancy blockade. This led to a hypothesis defining the steric properties of the alpha receptor and the active conformation of epinephrine at this receptor. However, two hydroxy substituted 1-aminotetralines ans two trihydroxytetrahydrosioquinoline derivatives, which were investigated to support this hypothesis, failed to show the predicted alpha adrenergic agonist activity. It is concluded that the interaction of certain 1-aminotetralines with a stereospecific binding site at the alpha receptor mimics occupancy blockade. However, this binding site is probably not entirely identical with the epinephrine binding site at the alpha receptor. Furthermore, the cyclic tetrahydroisoquinoline derivatives do not represent the active conformation of epinephrine at the receptor.