Abstract

Graded depression of the rate-increasing response of isolated guinea-pig atria to tyramine was observed after pretreatment (24 hours prior to the experiment) with graded doses of reserpine or reserpine-type alkaloids. This graded depression of the maximal response to tyramine constitutes the basis for a method which allows the quantitative estimation of the relative potencies of these agents. The relative potencies are in good agreement with those obtained by the use of technically more difficult and expensive methods (i.e., heart-lung preparation of the dog). The results are compatible with the view that a) tyramine releases norepinephrine from its stores, and b) this activity can be used as an indicator of the depletion by reserpine and reserpine-type alkaloids of the norepinephrine stores. The evidence indicates that this method can be applied only to closely related substances, that is, to agents with similar or identical mode of action.