Effects of ADTN and various other 2-aminotetralin derivatives on the efflux of 3H-dopamine from rat striatal slices.

Various compounds belonging to the 2-aminotetralin (2-amino-tetrahydronaphthalene) series were examined for their effects on the efflux of tritium from striatal and hypothalamic slices labelled with 3H-dopamine. Both 2-amino-6,7 dihydroxytetralin (ADTN) and 2-amino-5,6-dihydroxytetralin (iso-ADTN) increased tritium overflow in a concentration-dependent way (0.4 and 2.0 microM). Iso-ADTN was less potent than ADTN. Since these effects were inhibited by cocaine or nomifensine they are considered to reflect the propensity of these drugs to be transported into catecholaminergic nerve endings via the uptake carrier, subsequently displacing radiolabeled amine. The phenol derivatives of 2-aminotetralin (2 microM) were less effective than the catechols; their decreasing order of potency was 7-OH, 5-OH and 6-OH. The compounds 1-methyl-ADTN, 4-phenyl-ADTN and the dimethoxy-derivative of 2-aminotetralin were inactive. Of the mono and dihydroxy derivatives of N,N-dipropyl-2-aminotetralin the 7-OH and 6,7-diOH compounds only slightly affected tritium efflux, while the 6-OH, 5-OH and 5,6-diOH compounds (2 microM) were completely inactive. The data indicate that various 2-aminotetralin derivatives differ strongly in activity with regard to their interactions with the neuronal dopamine uptake system and the postsynaptic dopamine receptor, respectively.