RELATIVE PHARMACOLOGICAL EFFECTS OF 3-METHYL-3,4-DIHYDRO- AND 3-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 3-methyl-3,4-dihydro- and 3-methyl-1,2,3,4-tetrahydroisoquinoline derivatives, substituted in the 6,7 positions with dihydroxy, methylenedioxy and dimethoxy groups, were studied for their relative toxicological, circulatory and smooth muscle effects.

The secondary tetrahydroisoquinoline hydrochlorides were least toxic while the quaternary salts were most toxic. The substituents on the 6,7 positions had much less influence on toxicities than the substituents on the nitrogen. Exophthalmos was most pronounced with the methylenedioxy derivatives while tremors were observed only with the dimethoxy derivatives.

The substituents in the 6,7 positions had relatively little influence on the blood pressure response indicating that the pressor potency of the dihydroxy groups has been nullified by the 3-methylsubstituent. The quaterary ammonium salts were usually pressor while the secondary and tertiary compounds were diphasic depressor-pressors.

There was little evidence of tachyphylaxis in contrast to the results usually obtained with -phenylisopropylamines.

Vagotomy and atropine inhibited the pressor response of some of the pressors and vagotomy abolished the depressor phase of some of the mixed-acting compounds.

The epinephrine effect was usually potentiated. Respiration was usually initially stimulated. The pulse rate was usually decreased. The intestine was usually relaxed and the rabbit and guinea pig uteri were stimulated.