RELATIVE PHARMACOLOGICAL EFFECTS OF 1-METHYL-3,4-DIHYDRO- AND 1-METHYL-1,2,3,4-TETRAHYDROISOQUINOLINE DERIVATIVES

¹ From The Burroughs Wellcome & Co. U.S.A. Experimental Research Laboratories, Tuckahoe, N. Y.

A series of 1-methyl-3,4-dihydro- and 1-methyl-1,2,3,4-tetrahydroisoquinoline derivatives substituted in the 6 and 6,7 positions with hydroxy, methoxy and ethoxy groups and having in the 2 position hydrogen or methyl, were studied for their chemical and relative pharmacological properties.

The presence of hydroxy groups at positions 6 and 7 seemed to decrease toxicity. Usually the quaternary salts were more toxic than the secondary and tertiary amines.

The 1-methyl substituent had relatively little influence on the qualitative blood pressure responses; the effects of the present series were similar in most respects with those of the 1-unsubstituted analogs.

Tachyphylaxis of the pressor responses was occasionally noted.

Vagotomy and atropine did not influence the blood pressure responses.

Respiration was consistently stimulated. The pulse rate was usually unchanged.

Epinephrine was potentiated by the dihydroisoquinoline compounds and by the dihydroxy tetrahydroisoquinoline derivatives; it was inhibited by the other tetrahydro derivatives.

Tremors were observed with the majority of the compounds. Four of the tetrahydroisoquinoline derivatives produced strychnine-like convulsions.

The isolated intestine was either stimulated or relaxed or both by the dihydroxy derivatives but depressed by all other compounds. The uteri were consistently stimulated.