SOME TETRAHYDROISOQUINOLINES II. THEIR ACTION ON BLOOD PRESSURE, RESPIRATION AND SMOOTH MUSCLE

¹ From The Burroughs Wellcome and Company, U. S. A., Experimental Research Laboratories, Tuckahoe, New York

A number of isoquinolines have been studied in relation to their action on the blood pressure, pulse rate, respiration and smooth muscle, and an attempt has been made to relate their chemical constitution to their physiological action. Some of the principal conclusions from this study follow.

1. Pressor activity in these compounds is associated with the secondary amines rather than with the tertiary amines.

2. Hydroxy groups increase the pressor action while methoxy and ethoxy groups decrease it.

3. Pressor action is greatest when the hydroxy groups are placed in the 6,7 position. The above factors are the same as those which contribute to the pressor action of the isomeric -phenylethylmethylamines.

4. Depressor activity is associated with the tertiary amines.

5. Changing from a methoxy to an ethoxy group in the 6,7 position of the N-methyl compounds increases depressor action. This change is more important in the six position than in the five or the seven position.

6. Effects on the pulse were slight, except with N-methyl tetrahydroisoquinoline.

7. Respiratory stimulation was frequently observed with the N-methyl derivatives.

8. The hydroxy derivatives act on smooth muscle through the autonomic nervous system. The ethoxy derivatives usually depress smooth muscle, probably by a direct action, while the methoxy derivatives seem to possess both nervous and direct muscular actions.

9. N-methyl tetrahydroisoquinoline has the property of completely blocking the action of epinephrine on the motor ends of the sympathetic while leaving the inhibitor endings uninfluenced.

10. N-methyl-6-ethoxytetrahydroisoquinoline is an extremely active depressor agent, doses of 0.1 mgm. per kilogram lowering the blood pressure almost to zero for several hours. The animals survive, the heart action remains good and the blood pressure gradually returns to normal after three to four hours.

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