Interactions of amineptine with the neuronal dopamine uptake system: Neurochemicalin vitro andin vivo studies

Summary

The effects of amineptine on³H-dopamine uptake and 14C-dopamine release have been studied simultaneously in double labelling test performed on rat striatal synaptosomes.³H-dopamine uptake was completely inhibited at 10μM amineptine, a concentration which produced only a weak 14C-DA release (13% of the 14C-radioactivity stored). The IC 50 for the inhibition of³H-DA uptake was not modified by a previous treatment with reserpine whereas the IC 50 of (+) amphetamine and the IC 50 of clomipramine were decreased 9 fold and increased two fold, respectively. In binding studies on rat striatal membranes amineptine displacesin vitro the³H-GBR 12783, bound specifically to a component of the neuronal DA uptake complex. The apparent affinity of amineptine for this binding site was more than 150 times higher than its affinity for the binding site of³H-desipramine on rat cortical membranes. In mice, increasing doses of amineptine injected i. p. reduced in a dose dependent manner the specific retention of radioactivity in the striatum after an i. v. injection of a tracer dose of³H-GBR 12783. These data indicate that amineptine inhibits DA uptake and is virtually devoid of DA releasing effects. It displays a relatively low affinity for the NE uptake system. Its neurochemical profile in the double labelling test clearly differs from that of (+) amphetamine and from that of classical tricyclic anti-depressants.