Facile syntheses of potent dopaminergic agonists and their effects on neurotransmitter release

Abstract

The facile syntheses of important intermediates used in the preparation of the 2 potent dopaminergic agonists, 2-amino-6,7-dihydroxytetrahydronaphthalene (11) (ADTN) and its 5,6-dihydroxyl isomer 12 were described. 6,7-Dimethoxy-2-tetralone was prepared in 2 steps and 5,6-dimethoxy-2-tetralone in 3 steps both from commercially available materials. The effects of 11, 12 and the noncatechol analog, 2-aminotetrahydronaphthalene (ATN), on radioactive neurotransmitter release were studied in vitro using rat brain slices. Both 11 and 12, at a concentration of 2 .mu.M, caused a release of [3H]-DA [dopamine] and norepinephrine (NE), 11 being more potent than 12 in releasing [3H]-DA. ATN (2 .mu.M) was inactive in these experiments which showed the importance of the catechol function in this uptake-release process.