Bronchodilator Activity of Tyramine and its N-Methyl Derivatives. ∗

Abstract

There are few reported quantitative comparisons of the relative pressor and bronchodilator effects of chemicals in the epinephrine series, and it is an open question whether certain structural changes in such compounds may result in a relative increase of bronchodilator activity without a corresponding increase in pressor activity.

Tyramine, an extensively studied compound of this type, is a comparatively good pressor agent, but Jackson 1 reports that it does not exert any bronchodilator activity. He found, however, that horde-nine, the N-dimethyl derivative of tyramine, dilates the bronchi, although it exerts considerably less pressor activity. Thus, with these compounds there seems to be a differentiation between pressor and bronchodilator effects which is compatible with the evidence of Cannon and Rosenblueth 2 that the chemical mediators involved in the transmission of sympathetic stimulation to the bronchi and the blood vessels are not the same.

In the present work, a comparative study of the pressor and bronchodilator activities of the following compounds was made upon a series of 6 dogs and 4 cats, following technique already described. 3

1 β-4-Hydroxyphenylethyl amine (Tyramine).

2 β-4-Hydroxyphenylethyl methylamine (Methyl tyramine).

3 β-4-Hydroxyphenylethyl dimethylamine (Hordenine).

4 β-4-Hydroxyphenylethyl trimethyl ammonium iodide (Hordenine methiodide).

It was noted that, contrary to the finding of Jackson and others, tyramine actively dilates constricted bronchi in suitable preparations. Methyl tyramine is equally effective both as a pressor and bronchodilator and in some cases appears to be somewhat the more active. These effects were observed with doses as low as 0.001 millimols per kilogram, injected intravenously. Equimolecular dosage of hordenine is regularly without action on blood pressure or the bronchi but 5 to 10 times this dose usually gives responses comparable to those of tyramine. Since hordenine exerts an effect similar to that of nicotine, it probably acts through a different mechanism than tyramine which has no nicotine-like action. Likewise with hordenine methiodide, nicotine-like pressor and bronchodilator effects are readily observed and this compound is about 50 times more active than hordenine itself in both its pressor and bronchodilator activities. When hordenine and hordenine methiodide are injected into unpithed animals in equally effective doses with regard to pressor effects they produce equivalent stimulation of the respiration, thereby indicating also a close similarity in their nicotine-like stimulation of the central nervous system.

From the present work there seems to be no differentiation of relative pressor and bronchodilator activities in the series of compounds here studied, although a differentiation of the mechanism by which they produce these actions is indicated by a comparison of tyramine or its methyl derivative with hordenine or its methiodide.