Negative chronotropic and antiarrhythmic properties of atropine and other tropane analogues on isolated cat heart preparations.

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Abstract
This study was undertaken to characterize pharmacologically the negative chronotropic and antiarrhythmic action of atropine and other tropane analogues. Insight into the site of action of these drugs was obtained by comparing the effects on isolated heart preparations. Dose-response curves were constructed for the negative chronotropic action on the cat Langendorff preparation and refractory period prolongation determined by alteration in the maximal driving frequency of cat papillary muscles. In decreasing order, the relative potencies found in both preparations were: quinidine, l-atropine, d,l-atropine, d,l-homatropine, and l-scopolamine, and, with the exception of l-scopolamine, were quantitatively similar both for the production of bradycardia and for refractory period prolongation. At concentrations which produced a 20% decline in heart rate, tropane analogues reduced the rate of aconitine-induced tachycardia in cat Langendorff preparations to approximate the pre-aconitine control values. The similarity of potencies, found effective in all preparations, suggests that a prolongation of refractory period may be the basis for tropane-induced bradycardia as well as for its anti-aconitine action in cats. Neither tropine nor tropic acid, in concentrations as high as 10-3 to 10-2 M, altered the maximal driving frequency, nor did cocaine (8.8 .times. 10-8 to 8.8 .times. 10-5 M) influence either automaticity or rate of papillary muscles exposed to aconitine. Thus, at least part, if not all, of the negative chronotropic and antiarrhythmic effects of tropanes appears to be the result of a direct action on the myocardium. The concentrations of tropane alkaloids required to obtain these actions on cat myocardial preparations suggest they are probably within the therapeutic range.