Brain levels and metabolism of the dopaminergic agonist 2-amino-6,7-dihydroxytetrahydronaphthalene after administration of various prodrugs

The synthesis of four prodrug diesters (diacetyl, diisobutyryl, dipivaloyl, and dibenzoyl) of the potent dopaminergic agonist 2-amino-6,7-dihydroxytetrahydronaphthalene (6,7-ADTN) is described. The effects of prodrug structure on the levels of 6,7-ADTN in the rat corpus striatum and cerebellum, as well as the levels of the metabolite, 6-hydroxy-7-methoxy-2-aminotetralin, in the corpus striatum, have been determined after intraperitoneal administration. In addition, the striatal levels of 6,7-ADTN after administration of the dibenzoyl analogue via intraperitoneal, subcutaneous, and oral routes have been measured. These prodrugs produce a significant improvement in the penetration and accumulation of 6,7-ADTN in the brain.