STUDIES ON VERATRUM ALKALOIDS: XIX. THE ACTION OF VERATRAMINE UPON CARDIOACCELERATION CAUSED BY EPHEDRINE, TYRAMINE, PHENYLEPHRINE AND ISOPROPYLARTERENOL

¹ Department of Pharmacology, Harvard Medical School, Boston 15, Massachusetts

1. The positive chronotropic action of ephedrine was determined quantitatively in the heart-lung preparation of the dog. The dose causing 50 per cent of maximal acceleration (ED50) under the conditions of the present experiments is 0.20 mgm. (range 0.11-0.33 mgm. in 10 experiments). The dose of ephedrine causing maximal acceleration of the heart very closely approximates 2 mgm.

2. The positive chronotropic action of ephedrine is antagonized by veratramine. Under the conditions of maximal rate effect by 2-3 mgm. ephedrine the dose of veratramine causing 50 per cent inhibition of acceleration (I₅₀) is 0.28 mgm. (range 0.24-0.33 mgm. in 7 experiments).

3. Pretreatment of the heart with doses of 0.3 to 3.0 mgm. veratramine reduces the rate attained with the dose causing maximal acceleration and also reduces the absolute value of maximal acceleration, but does not prevent ephedrine from exerting positive chronotropic action. Pretreatment with 0.1-1.0 mgm. veratramine does not change the dose causing maximal acceleration and does not. alter position or slope of the log dose-response curve of the positive chronotropic activity of ephedrine. Pretreatment with 3 mgm. veratramine makes ephedrine less active and changes the slope of the log dose-response curve.

4. Atropine does not noticeably alter the positive chronotropic action of ephedrine either in the normal heart or in the heart pretreated with veratramine.

5. The positive chronotropic action of ephedrine can be separated from its positive inotropic action by veratramine.

6. The positive chronotropie action of the aromatic amines tyramine, phenylephrine and isopropylarterenol is antagonized by veratramine in qualitatively the same way as the cardioaccelerator action of epinephrine, norepinephrine or ephedrine.