Effect of sympathomimetic amines on the synaptosomal transport of noradrenaline,dopamine and 5-hydroxytryptamine

The interaction of sympathomimetic amines with the transport of ³H-noradrenaline (³H-NE), ³H-dopamine (³H-DA) and ³H-5-hydroxytriptamine (³H-5-HT) were investigated in rat hypothalamic (³H-NE) and striatal (³H-DA and ³H-5-HT) synaptosomes. Modifications in the phenylethylamine structure led to changes in activity towards biogenic amine uptake and release: (a) the introduction of a β-OH group led to compounds less active in inhibiting uptake and stimulating release of ³H-NE, ³H-DA and ³H-5-HT, with the exception of ³H-NE release which was stimulated more by unlabeled 1-NE than by DA; (b) the introduction of phenolic -OH groups always led to compounds which were stronger uptake inhibitors and releasers of the three biogenic amines; (c) the α-methylation increased the potency towards uptake inhibition and release stimulation, with the exception of ³H-NE release: in fact, the releasing activity of phenylethylamine was suppressed by α-methylation; (d) the introduction of a -Cl group in the para position selectively potentiated the effects on ³H-5-HT uptake and release and generally depressed those on catecholamine transport.