Blockade by triptyline compounds of tyramine uptake and of tyramine-induced phosphorylase activation in cardiac tissue

Abstract

Pretreatment of rats with amitriptyline, nortriptyline, or protriptyline significantly decreased the effect of tyramine on cardiac phosphorylase and also significantly decreased the uptake of tyramine-³H as measured by the amount of octopamine-³H found in the heart. The order of efficacy of the drugs in blocking both the effect and the uptake of tyramine was protriptyline > nortriptyline > amitriptyline. The compounds studied have been reported to have this same order of efficacy in blocking the uptake of norepinephrine or in enhancing the norepinephrine response. The data presented support the hypothesis that tyramine utilizes the same uptake system as does norepinephrine and that drugs which enhance the effects of norepinephrine and decrease the effects of tyramine do so by preventing the uptake of the amine. The data also support the concept that within a chemical series the secondary amine is more effective than the corresponding tertiary amine in blocking adrenergic amine uptake.