THE COMPARATIVE PHARMACOLOGY OF THE ISOMERIC CHAIN METHYL SUBSTITUTED HEPTYLAMINES

¹ Department of Pharmacology, West Virginia University School of Medicine, Morgantown, W. Va.

1. The vasopressor activity of a series of chain methyl substituted 2-heptylamines including 3-octylamine, 2-methyl-2-heptylamine, 3-methyl-2-heptylamine, 4-methyl-2-heptylamine, 5-methyl-2-heptylamine, 6-methyl-2-heptylamine, and 2-octylamine has been determined in anesthetized and unanesthetized dogs and compared with 2-heptylamine and epinephrine. The compounds range from agents with almost no pressor action to 2-methyl-2-heptylamine, 5-methyl-2-heptylamine, and 6-methyl-2-heptylamine which are about 1/250 as active as epinephrine or almost as active as 2-heptylamine. Repeated administration of the more potent agents does not rapidly produce tachyphylaxis as is the case with the phenisopropylamine derivatives.

2. With the exception of 2-heptylamine, all of these agents produce a decrease in tone in the isolated rabbit jejunum with a concentration of 10 mgm./100 cc. that is comparable to that produced by 0.5-1.0 microgm. epinephrine per 100 cc. The most relaxant agents are 2-octylamine and 3-methyl-2-heptylamine.

3. All of the agents are about 1/25,000 as active as epinephrine in dilating the isolated guinea pig tracheal chain, with 3-octylamine and 2-octylamine slightly more active than the other agents.

4. All of the agents cause the death of white mice when given intraperitoneally in the dose range of 100-200 mgm./kgm. to individual mice kept at 24-25°C. and produce erection of hair, exophthalmos, and increased motor activity with the exception of 3-octylamine. Necropsy indicated the presence of hemorrhagic spots in the lungs of over half the mice dying at a given dose of drug. 2-Methyl-2-heptylamine and 4-methyl-2-heptylamine are most toxic and 2-heptylamine, 3-methyl-2-heptylamine, and 2-octylamine are least toxic.