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Journal of Pharmacology And Experimental Therapeutics, Vol. 79, Issue 3, 215-224, 1943
Copyright © 1943 by American Society for Pharmacology and Experimental Therapeutics

STUDIES ON VERATRUM ALKALOIDS IV. THE SITES OF THE HEART RATE LOWERING ACTION OF VERATRIDINE

OTTO KRAYER 1, EARL H. WOOD 1, and GONZALO MONTES 1

1 From the Department of Pharmacology, Harvard Medical School, Boston

In cross-circulation experiments in which the heart-lung system was in connection with the central nervous system by nervous pathways only, the veratrum alkaloid veratridine, when administered into the heart-lung circulation, caused a decrease in heart rate in a dose too small to have a direct action upon the impulse generation in the heart. This effect of veratridine was found to be mediated by the vagus, the afferent impulses originating within the heart-lung circuit. A heart rate decrease could also be obtained when the alkaloid was injected into the circulatory system of the head. The available evidence indicates that afferent impulses responsible for the reflex decrease do not arise in the heart or lungs alone, but also in the carotid sinus area, and that there is in addition to the reflex effect a direct effect upon the central nervous system causing vagal stimulation.

For a study of the reflex response originating in the heart-lung circulation it was found imperative to work with dosages close to the minimal effective dose, as large initial doses diminished or abolished a subsequent response. With the dosages used, such a weakening was not observed with regard to the central effect.

The reflectoric as well as the central heart rate lowering effect were caused by the ester-alkaloid veratridine but not by either of the two products of its hydrolysis, cevine and veratric acid.

Submitted on July 15, 1943




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Copyright © 1943 by the American Society for Pharmacology and Experimental Therapeutics.