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- W2052460192 abstract "Ten beta-adrenoceptor blocking drugs varying in lipophilicity and beta-adrenoceptor blocking potency were examined for inhibitory effects on synaptosomal [3H]noradrenaline uptake. All compounds produced a concentration-dependent inhibition of noradrenaline uptake, but were at least one order of magnitude less potent than desmethylimipramine and cocaine. The order of potency was pronethalol greater than propranolol greater than betaxolol greater than alprenolol greater than oxprenolol greater than practolol greater than metoprolol greater than acebutolol greater than sotalol greater than atenolol, with IC50 values ranging from 4.0 X 10(-6) to 2.2 X 10(-3) M. Uptake inhibition was unrelated to beta-adrenoceptor blocking potency, but was highly correlated with drug lipophilicity. (+)-Propranolol was an effective uptake inhibitor, as was the local anaesthetic procaine. Kinetic analysis of uptake inhibition by propranolol, oxprenolol, metoprolol and procaine revealed a mixed inhibition for all four agents examined. It is suggested that this effect of beta-adrenoceptor blockers may be mediated, at least in part, by an action on membrane phospholipids associated with the noradrenaline carrier protein, and that noradrenaline uptake inhibition may underlie certain central side-effects observed with some drugs in this group." @default.
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- W2052460192 date "1984-07-01" @default.
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- W2052460192 title "Inhibition of synaptosomal [3H]noradrenaline uptake by β-adrenoceptor blocking drugs: Influence of lipophilicity" @default.
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- W2052460192 doi "https://doi.org/10.1016/0014-2999(84)90263-2" @default.
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