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- W2051256007 abstract "Abstract Rat brain striatal synaptosomes or slices in vitro have been used to test the DA uptake inhibitory or releasing properties of certain drugs and to differentiate between these two processes. DA uptake into synaptosomes rapidly reaches saturation and the choice of incubation time is important for measuring inhibition. Thus nomifensine is apparently less active as an inhibitor when the incubation time is extended beyond the linear phase of uptake. As overall DA uptake reaches a plateau an extensive exchange of DA still occurs, presumably through a process of spontaneous release and reuptake. This phenomenon may provide an explanation for the apparent releasing properties of uptake inhibitors, the action of which would tend to favour the spontaneous release. Both nomifensine and amphetamine in high concentrations cause an increase in the amount of radioactivity in the medium when they are incubated with synaptosomes preloaded with [3H)DA. Their combined effects, however, are not additive, showing that different mechanisms must be involved. The difference is emphasised when the drugs are introduced under superfusion conditions where reuptake of DA is minimised. Amphetamine shows a very strong releasing effect, whereas nomifensine is inactive. Benztropine and methylphenidate both behave like nomifensine in these conditions. Similar results are found using preloaded, electrically-stimulated striatal slices, but in this case methylphenidate, as well as amphetamine, increases the overflow of radioactivity. With respect to newly-accumulated [3H]DA, nomifensine and benztropine can thus be considered as purely uptake inhibitors. The different releasing properties of methylphenidate and amphetamine may provide an explanation for their pharmacological differences." @default.
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- W2051256007 date "1979-07-01" @default.
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- W2051256007 title "Dopamine uptake inhibitors and releasing agents differentiated by the use of synaptosomes and field-stimulated brain slices in vitro" @default.
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- W2051256007 doi "https://doi.org/10.1016/0006-2952(79)90217-x" @default.
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