The effect of psychostimulants on [3H]dopamine uptake and release in rat brain synaptic vesicles

Summary. Amphetamine and its derivatives are psychostimulants active at the plasma membrane monoamine transporters. In the present study we assessed the interaction of parachloroamphetamine, D-amphetamine, fenfluramine and methylendioxymethamphetamine with brain vesicular monoamine transporter using purified rat striatal synaptic vesicles. All four psychostimulants inhibited vesicular [³H]dopamine uptake in a competitive and dose-dependent manner and had no effect on [³H]dihydrotetrabenazine binding. At higher concentrations the drugs enhanced [³H]dopamine vesicular efflux. Parachloroamphetamine was the most potent agent while methylendioxymethamphetamine was the weakest one. The vesicular activities may be relevant to their neurotoxicity.