Interactions between cocaine, tyramine and noradrenaline at the noradrenaline store.

In the cat, the pressor actions of noradrenaline and of adrenaline were generally reduced and that of tyramine was increased during infusions either of noradrenaline or of adrenaline. The increase in the response to tyramine after an infusion of noradrenaline was prevented by cocaine, methyl phenidate and pipradrol. Pipradrol, unlike its isomer azacyclonol, increased the responses to catechol amines but reduced that to tyramine. Cocaine did not prevent the increase in the noradrenaline content of cat kidney and uterus after an infusion of noradrenaline. In the pithed rat, cocaine increased the pressor response to noradrenaline but antagonized that to tyramine. Treatment of the rat with reserpine prevented the effect of cocaine on the response to tyramine but did not modify the potentiation of the response to noradrenaline. Prolonged treatment with cocaine did not lower the tissue noradrenaline levels and did not prevent the noradrenaline depletion by reserpine. It is suggested that interactions between cocaine, tyramine and noradrenaline occur at the point where noradrenaline enters its tissue store.