STUDIES ON VERATRUM ALKALOIDS

VI. PROTOVERATRINE: ITS COMPARATIVE TOXICITY AND ITS CIRCULATORY ACTION

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

In acute toxicity experiments in mice with intravenous administration, protoveratrine, a triacyl ester of protoverine, was found to be ten times more toxic than veratridine, a monoacyl ester of cevine. The alkamines jervine, rubijervine, cevine, germine, and protoverine were very much less toxic than the ester alkaloids. Conspicuous qualitative differences exist between the alkaloids and the alkamines as groups as well as between the individual members of the two groups.

In conformity with its sterol nature and chemical relation to the cardiac glycosides, protoveratrine causes a systolic standstill in the isolated frog heart and positive inotropic (therapeutic) effect in the hypodynamic frog heart, as well as in the isolated failing mammalian heart. The minimal effective therapeutic dose is somewhat smaller than that of veratridine. The minimal toxic dose leading to irregularities of the heart rate is very much smaller than that of veratridine. Effective inotropic doses of protoveratrine not leading to irregularities of rate do not decrease the heart rate of the denervated heart; this is contrary to what was observed with veratridine. In the innervated heart, however, decrease in heart rate is produced which is partly due to reflex action and partly due to central action, as was observed with veratridine.

In the intact circulation of the dog the outstanding effect of small dosages (0.5 to 2.5 micrograms per kgm.) is a blood pressure decrease which is due in part to a heart rate decrease and in part to a decrease in arterial resistance.

The vasodilatation as studied in the femoral artery is reflex in nature, intraarterial injections of dosages leading to much higher arterial concentrations than would ever occur with intravenous administration having no effect.

As was observed with veratridine, large dosages of protoveratrine cause release of epinephrine from the suprarenal gland, which is an important element in the vasopressor effect.

Tachyphylaxis to the cardiodecelerator effect as well as to the depressor effect develops much more readily with protoveratrine than with veratridine.

This article has been cited by other articles:

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