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.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D003342:Corpus Striatum / Q000378:metabolism; D004355:Drug Stability; D005260:Female; D009281:Naphthalenes / Q000008:administration & dosage* / Q000138:chemical synthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000378:metabolism; D013997:Time Factors
D009281:Naphthalenes; D013764:Tetrahydronaphthalenes; C011639:ADTN