Effects of various isoquinoline alkaloids on in vitro H-3-dopamine uptake by rat striatal synaptosomes

Various alkaloids having an isoquinoline skeleton from different species of the Annonaceae, Fumariaceae, and Aristolochiaceae (aporphine, cularine, benzylisoquinoline, and bisbenzylisoquinoline derivatives) were rested for their ability to inhibit in vitro H-3-dopamine uptake by rat striatal synaptosomes which was compared to their activity ac striatal dopamine D-1 H-3-SCH 23390 and D-2 H-3-raclopride binding sites. Except for some aporphine derivatives (anonaine [1], norstephalagine [2], isopiline [3]) and some bisbenzylisoquinoline alkaloids (dimethylgrisabine [27], antioquine [28], obaberine [29], isotetrandrine [30])that displayed affinities of the same order as reference compounds (nomifensine [38], amineptine [39], dexamphetamine [40]), the other tested products had low, or no, affinity on H-3-dopamine uptake. Only anonaine [1] appeared to display a goad selectivity for 3H-dopamine uptake since, in comparison, its affinity ac dopamine D-1 H-3-SCH 23390 and D-2 H-3-raclopride binding sites was low. These data suggest chat ir. could be possible to synthesize anonaine-like products displaying intense dopamine-uptake inhibitory properties, which could lead to a potential antidepressant activity.