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-hydroxytryptamine (3H-5-HT) were investigated in rat hypothalamic (3H-NE) and striatal (3H-DA) and 3 H-5-HT) synaptosomes. Modifications in the phenylethylamine structure led to changes in activity towards biogenic amine uptake and release: (a) the introduction of a beta-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 alpha-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 alpha-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.
D000818:Animals; D001692:Biological Transport; D003342:Corpus Striatum / Q000378:metabolism / Q000648:ultrastructure; D003864:Depression, Chemical; D004298:Dopamine / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism / Q000648:ultrastructure; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000378:metabolism*; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013566:Sympathomimetics / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D010627:Phenethylamines; D013566:Sympathomimetics; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine