EFFECT OF L-DEPRENYL, ITS STRUCTURAL ANALOGS AND SOME MONOAMINE-OXIDASE INHIBITORS ON DOPAMINE UPTAKE

The effect on dopamine uptake by L-deprenyl, its structural analogues and different types of monoamine oxidase (MAO) inhibitors was investigated. Both direct [H-3]dopamine uptake into rat striatal slices and binding of a specific dopamine uptake inhibitor [H-3]GBR-12935 were used in the present study. L-Deprenyl exhibits a relatively weak dopamine uptake inhibitory effect in vitro, while D-deprenyl possesses a very potent inhibitory effect. The potent effect of D-deprenyl on dopamine uptake may be responsible, at least in part, for its behavioral effects and abuse liability. L-Methamphetamine, a metabolite of L-deprenyl, does not inhibit [H-3]GBR-12935 binding but it reduces the retention of [H-3]dopamine in striatal tissues, suggesting that it may enhance dopamine release. The MAO-A inhibitors clorgyline and brofaromine also exhibit dopamine uptake inhibitory effects. Irreversible and reversible MAO-B inhibitors, however, such as pargyline, aliphatic N-methylpropargylamines, Ro 19-6327 and MDL-72974A and MAO-A inhibitor moclobemide do not possess any appreciable inhibitory effects on dopamine uptake. Dopamine uptake is probably unrelated to the pharmacological actions of L-deprenyl.