A. Hjort, E. J. Debeer, J. S. Buck
Sep 1, 1942
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Journal
Journal of Pharmacology and Experimental Therapeutics
Abstract
Three homologous series of 2 -alkyl- 1,2,3,4 -tetrahydroisoquinoline hydrochlorides having 6,7 -dihydroxy-, 6,7 -dimethoxy- and 6 -ethoxy- substituents were studied with respect to toxicity and relative circulatory and smooth muscle effects. Toxicity increased as the length of the 2 -alkyl chain increased. The 6,7 -dihydroxy derivatives were least toxic and the 6,7 -dimethoxy group was most toxic. The 6,7 -dihydroxy group resembled well-known pressor compounds in the production of pilomotor effects, exophthalmos and salivation. The methoxy and ethoxy groups produced coarse tremors instead of sympathomimetic symptoms. The hydroxy-substituted compounds were pressors: the shorter carbon chain compounds had the greater potency and duration. The methoxy-substituted compounds were depressors; the longer carbon chain compounds had the greater potency. The ethoxy-substituted compounds had biphasic depressor-pressor action with small doses and were usually depressor with large doses. Tachyphylaxis was observed with some of the pressors. Vagotomy and atropine had no influence on the blood pressure response. Respiratory effects were inconsistent. Pulse rates were usually slowed. The epinephrine response was not affected by the hydroxy derivatives but was inhibited by methoxy and ethoxy derivatives. Smooth muscle effects were qualitatively consistent. The isolated intestine was relaxed and the rabbit and guinea pig uteri were stimulated by all the compounds. The 6,7 -dihydroxy derivatives stimulated the intestine and uterus of the intact cat and rabbit.