THE CARDIOVASCULAR EFFECTS OF TETRANDRINE AND DEMETHYL-TETRANDRINE

The analgesic, antiphlogistic, anti-anaphylactoid shock and anti-amebic effects of tetrandrine and demethyl-tetrandrine have been reported previously. Further studies on their cardiovascular effects were undertaken with the following results: (1) By intravenous and intramuscular injection as well as per oral administration, tetrandrine and demethyl-tetrandrine caused a profound hypotensive effect in urethan-anesthetized cats. The hypotensive effect of tetrandrine was found to be stronger and more sustained than that of demethyl-tetrandrine. The blood pressure was reduced by more than 50% in the case of tetrandrine and the effect lasted for several hours at a dose of 3 mg/kg regardless of its route of administration. (2) Large doses of the two alkaloids, when injected intravenously, but not intramuscularly, caused a decrease in the contractile force of the cat's heart, which returned to normal within 2-5 minutes. (3) During the fall of the blood pres ure induced by tetrandrine and demethyltetrandrine, the splenic volume of the animals was invariably increased, but it might be reduced in size when the fall of blood pressure was abrupt and severe. (4) These two alkaloids, 1.5-3.0 mg/kg given intravenously, did not cause any significant change in EKG except the reduction of the amplitude of the R wave. The P-R interval was unaltered but sometimes it became shortened under tetrandrine and lengthened under demethyl-tetrandrine; (5) In perfused isolated rabbit's ears, these two alkaloids showed direct vasodilating effects, the minimal effective concentrations of tetrandrine and demethyl-tetrandrine being 1:20,000 and 1:4,000 respectively. In equimolar concentrations, the vasodilating effect of tetrandrine was more prominent and lasted for a longer time in contrast with papaverine. (6) In perfused isolated rabbit's ears with the innervation intact, these two alkaloids and papaverine, at the dosage of 3 mg/kg intravenously, produced reflex vasodilatation. The effect of tetrandrine appeared to be the strongest and lasted the longest, papaverine being the weakest.