Dopamine uptake inhibiting versus dopamine releasing properties of fencamfamine: an in vitro study.

To elucidate its mechanism of action, the effects of fencamfamine, a norcamphanethylamine derivative, were studied in vitro on the release of newly accumulated dopamine in superfusion experiments using slices of rat corpus striatum and substantia nigra in comparison to nomifensine and d-amphetamine. Furthermore, the activity of fencamfamine on biogenic amine uptake in synaptosome preparations and on monoamine oxidase activity was evaluated. As compared to d-amphetamine, fencamfamine exhibited roughly 10 times less dopamine releasing activity in striatal slices at concentrations at which dopamine uptake into synaptosomes was almost completely blocked although, at high concentrations, what was probably non-specific release due to interactions with neuronal membranes could also be demonstrated. In addition, fencamfamine, unlike d-amphetamine did not inhibit monoamine oxidase. It is concluded that, at least in the models employed, the in vitro profile of fencamfamine is more similar to that of nomifensine, a reportedly pure uptake inhibitor, than to d-amphetamine.