Inhibition of Cardiac Effects of Noradrenaline by Eleven Indole Alkaloids, Two Azepinoindoles, Quinidine, Quindonium, and Propranolol

Abstract

Most of the indole alkaloids of the Iboga and Voacanga series (Apocynaceae) exert strong negative chrono- and inotropic actions which are, however, neither cholinergic nor strictly quinidine-like.These actions on the heart are reminiscent of those of many beta-adrenergic blocking drugs and made it necessary to investigate whether these alkaloids would inhibit the normal ino- and chrono- tropic effects of noradreneline (NA). It was possible that the depressing cardiac actions of these alkaloids would diminish the positive NA effects by purely functional antagonism. In this case, the anti-adrenergic activity of the alkaloids should be correlated with their depressing activity, and, consequently, the great influence of chemical structure on pharmacological activity found previously for these compounds should be, at least qualitatively, the same for direct and anti-adrenergic actions.
As in our previous experiments the synthetic azepinoindoles ETAI and Methoxy-ETAI, quinidine, and quindonium were used for comparison, and propanolol served now as a typical beta-receptor blocking drug.

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