THE COMPARATIVE PHARMACOLOGY OF THE ISOMERIC NITROGEN METHYL SUBSTITUTED HEPTYLAMINES

¹ Department of Pharmacology, West Virginia University School of Medicine, Morgantown

1. The vasopresor activity of 3-heptyl, 2-methyl-2-hexyl, 3-methyl-2-hexyl, 4-methyl-2-hexyl, 5-methyl-2-hexyl, and 2-heptyl methylamine hydrochloride in dogs anesthesized with sodium thiopental and scopolamine has been determined and compared with the corresponding unsubstituted heptylamine hydrochloride and epinephrine. Nitrogen-methyl substitution does not significantly influence the vasopressor activity as compared with the unsubstituted amines and the compounds range from agents with very short duration of action and almost no pressor action to 4-methyl-2-hexyl methylamine which is about 1/200 as active as epinephrine and has a duration of action. The 2-heptyl methylamine is almost as active, and the corresponding unsubstituted amines may be slightly more active.

2. Nitrogen methylation of the isomeric heptylamines decrease the spasmogenic activity of the unsubstituted heptylamines on isolated rabbit jejunum or increases the relaxant activity.

3. All of the agents cause the death of white mice whengiven intraperitoneally in the dose range of 60-185 mgm./kgm. to individual mice kept at 22-23°C, and produce erection of hair, exophthalmos, increased motor activity and convulsions. Nitrogen methylation did not uniformly increase or decrease the toxicity of any given agent.

4. Oral doses of 3 mgm. of 4-melthyl-2-hexyl methylamine, 4-methyl-2-hexylamine, 2-heptyl methylamine, and 2-heptylamine hydrochloride per kgm. produce marked vasopressor effects and have typical sympathomimetic actions. The 4-methyl-2-hexyl compounds were more active than the 2-heptyl derivatives. tives.