STUDIES ON VERATRUM ALKALOIDS

VIII. Veratramine, an Antagonist to the Cardioaccelerator Action of Eprinephrine

¹ Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

Veratramine, a secondary base of the veratrum alkaloid series, antagonizes the cardioaccelerator (or positive chronotropic) action of epinephrine in the isolated, denervated heart (HLP) of the dog, as well as in the whole circulatory system of dogs and cats under anesthesia, or of spinal or completely pithed cats.

The site of action is in the pacemaker tissue of the heart. Atropine in large doses does not modify this veratramine effect.

The action of epinephrine upon contractility (positive inotropic action) is not abolished by doses of veratramine which annul the cardioaccelerator action. It is thus possible to separate the two fundamental elements of the cardiac action of epinephrine.

The vasodilator action of epinephrine upon the coronary vessels of the denervated isolated heart (HLP) of the dog, and the vasopressor action of epinephrine in the whole circulation are not abolished by doses of veratramine which have a very marked effect upon heart rate.

The hitherto known antagonists of epinephrine, which abolish or prevent its vasopressor action, are devoid of the property of veratramine, when they are subjected to study under identical conditions.

Of several other veratrum alkaloids studied, jervine, another secondary base, and the glycosides, veratrosine and pseudojervine, were also found capable of antagonizing the cardioaccelerator effect of epinephrine.