Breoganine

Various alkaloids having an isoquinoline skeleton from different species of the Annonaceae, Fumariacae, and Aristolochiacae (aporphine, cularine, benzylisoquinoline, and bisbenzylisoquinoline derivatives) were tested for their ability to inhibit in vitro 3H-dopamine uptake by rat striatal dopamine D1 3H-SCH 23390 AND D2 3H-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 the reference compounds (nomifensine [38], amineptine [39], dexamphetamine [40]), the other tested products had low, or no, affinity on the 3H-dopamine uptake since, in comparison, its affinity at dopamine D1 3H-SCH 23390 and D2 3H-raclopride binding sites was low. These data suggest that it could be possible to synthesize anonaine-like products displaying intense dopamine-uptake inhibitory properties, which could lead to a potential antidepressant activity.

Five natural cularines isolated from the aerial parts of Sarcocapnos crassifolia (Fumariaceae) and a cularioid isolated from the bark of Guatteria ouregou (Annonaceae) were tested for their ability to displace ³H-SCH 23390 and ³H-raclopride from their striatal binding sites.Celtisine, breoganine and cularidine were able to inhibit the binding at D-1 and D-2 dopaminergic sites at nanomolar concentrationsOther alkaloids were active at micromolar concentrationsThese data suggest that the presence of an oxepine system in the isoquinoline skeleton could lead to compounds which would be very active and possibly selective at dopaminergic receptor sites.