Comparative Studies of Protoveratrine A and Protoveratrine B Intravenously in Hypertensive Man

Abstract

Comparative studies of intravenously administered protoveratrine A and protoveratrine B in hypertensive man indicate that the alkaloids have qualitatively similar hypotensive, bradycrotic, and emetic actions, but quantitatively different hypotensive and emetic potency. The relative hypotensive potencies of the two substances were determined by analyses of logarithmic dose-response curves in the same patients. On a weight basis protoveratrine B was slightly less potent than protoveratrine A. A favorable dissociation between hypotensive and emetic activity was found. Tolerance ratios were determined in which the largest doses of protoveratrine B given without nausea were compared with the doses of protoveratrine A producing nausea. These ratios were adjusted for the differences in hypotensive potency of the alkaloids. Protoveratrine B was better tolerated than protoveratrine A ( p <.001). Indeed, protoveratrine B had little emetic activity when given intravenously in doses producing normotension. Protoveratrine B appears to have properties that warrant its preferential selection for parenteral administration. Its effective dosage range has been studied. The strong hypotensive activity of intravenously administered protoveratrine B, its development of maximal action within minutes, and its pulse-slowing effect favor its use in those hypertensive states in which almost immediate lowering of the blood pressure is indicated. Fixed hypertension lends itself to the application of biological assay technics. The use of such technics in human pharmacology fosters the perception of clinically significant differences among drugs that are chemically closely related.