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Blinks JR. 
“Evaluation of the cardiac effects of several beta adrenergic blocking agents”. 
Ann N Y Acad Sci. 1967 Feb 05;139(3):673-85.
Abstract
Our experiments with beta adrenergic blocking agents have been prompted by three related interests. The first of these is the question of the separability of the positive chronotropic and inotropic effects of the sympathomimeticamines. That is, are the effects of these substances on the strength and frequency of contraction of the heart mediated through interaction with a single receptor type, or are there separate, differentiable populations of receptors for the two effects? The study of the actions of adrenergic blocking agents provides one obvious approach to this question. The second interest has been in the nature of the antagonism between the various beta adrenergic blocking agents and the catecholamines at the cardiac adrenergic receptors. We wanted information about such factors as the specificity and surmountability of the antagonism, the nature of the shifts produced in the dose-effect curves, and the time course of onset of blocking action. The third interest has been in the relation between the adrenergic blocking actions and other cardiac effects of some of the more promising new beta adrenergic blocking drugs. In high concentrations, all of these substances have negative inotropic and chronotropic effects in lower concentrations, some of them-perhaps all-have sympathomimetic effects in some degree. As an experimental tool, a cardiac adrenergic blocking agent is clearly more useful the greater the range of concentrations over which it exerts its blocking action without producing other effects.
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