Negative Chronotropic and Atrioventricular Blocking Effects of Taxine on Isolated Frog Heart and Its Acute Toxicity in Mice

Abstract

The alkaloid mixture of yew (Taxus baccata) was converted to sulphate salt and this salt form of the drug was used throughout the experiments. The median lethal doses (LD50) and their 19/20 confidence limits of two samples of the drug, the freshly prepared and the stored taxine sulphate, were determined on mice (s. c.) and found as 12.96 (11.37-14.77) and 13.09 (11.73-14.61) mg/kg, respectively. There was no significant difference between these values. Results show that taxine in salt form can be preserved for long periods without loosing its properties. The cardiac actions of the drug (10-100 µg/ml) were determined on isolated frog heart. It was found that the drug slows both atrial and ventricular rate dose-dependently, however, the rate-depressing effect was more prominent on the ventricle, e.g., in the highest concentration, the observed percent changes in cardiac rate (mean ± S.E.M.) were 38.29 ± 4.13 for atrium and 1.71 ± 0.80 for ventricle, indicating that the atrioventricular conduction is more susceptible to the drug. The effect of the drug on the heart could be removed partially by washing. At the end of this procedure, the atrial and ventricular rates reached 56.63 ± 5.44 and 51.35 ± 5.54 that of control rates, respectively. From these findings and those observed by previous authors, it is deduced that the actions of taxine on heart might result from its Ca²⁺ antagonizing properties, but electrophysiological studies are necessary for a definitive conclusion.