5-, 6-, 7- and 8-amino-2-(N,N-di-n-propylamino)-1,2,3,4-tetrahydrophthalenes: Centrally acting DA and 5-HT(1A) agonists

Article abstract of DOI:10.1016/0223-5234(93)90028-D

5-, 6-, 7- and 8-Amino-2-(N,N-di-n-propylamino)-1,2,3,4-tetrahydronaphthalene were synthesized and compared with the corresponding phenolic compounds in vivo and in vitro for their effects on central serotonergic (5-HT(1A)) and dopaminergic (D₂) systems. The 5- and 8-amino isomers surprisingly showed a 100-fold lower affinity for D₂ and 5-HT(1A) receptors, respectively, than their corresponding phenols. This was also reflected in vivo. The 6-amino- and hydroxy-isomers were equipotent, while the 7-amino compound showed in vivo effects both on dopaminergic and serotonergic systems, the latter not being noticed in vitro. Intermediates 8-bromo-2-(N,N-di-n-propylamino)-1,2,3,4-tetrahydronaphthalene and 2-(N,N-di-n-propylamino)-1,2,3,4-tetrahydronaphthalene-8-carboxylic acid methyl ester were also tested and found to be quite potent 5-HT(1A) agonists.