STUDIES ON VERATRUM ALKALOIDS

XIII. Metabolic Action of Veratridine and of the Secondary Amine Bases Veratramine, Veratrosine, and Pseudojervine on Cardiac Tissue of the Rat

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

Using the Warburg method experiments were conducted on the effect of veratrum alkaloids upon the metabolism of atrial tissue and of homogenates from ventricle muscle of the rat heart. There is a marked difference between the metabolic action of veratridine, the veratric acid ester of cevine, belonging to the tertiary amines, and the metabolic action of the secondary amines, veratramine, veratrosine and pseudojervine.

Veratridine causes an increase in oxygen uptake which is followed by an inhibition of respiration. This effect, which is brought about in the atrial tissue by concentrations 1 to 8 x 10^-4 M, is dependent upon the structural integrity of the cell. In homogenates veratridine has little or no activity. This is in agreement with previous observations in ventricular muscle of the guinea pig (3).

Veratramine in a concentration of 1 x 10^-4 M with glucose, lactate, or pyruvate as substrate inhibits respiration to 50 per cent without initial augmentation of oxygen uptake. This effect occurs in the "intact" atrial tissue to the same extent as in the homogenate of ventricle muscle. Anaerobic glycolysis is not inhibited. The inhibition occurs in the oxidative phase of glucose metabolism. Oxidation of lactic acid, pyruvic acid and fumaric acid is likewise inhibited. The cytochrome oxidase system and succinic dehydrogenase are not influenced.

Veratrosine, the glycoside of veratramine, and pseudojervine, the glycoside of the secondary amine base, jervine, act qualitatively like veratramine but are less potent.