THE PHARMACOLOGIC ACTION OF ERGOTOCIN, A NEW ERGOT PRINCIPLE

¹ From the Department of Obstetrics and Gynecology, University of Chicago, and the Lilly Research Laboratories, Indianapolis

1. Ergotocin, a new ergot base, has a powerful oxytocic action on both isolated and puerperal mammalian uteri. Its effect is prompt and persistent, and can be specifically demonstrated in human postpartum uteri by intravenous, intramuscular, oral, or sublingual administration. Doses varying from 0.1 to 0.25 mgm. given by vein are sufficient to produce a typical response.

2. Ergotocin may be primarily assayed by the U. S. P. cock's comb method and by the isolated uterine response (not the Broom-Clark method). It should be finally assayed on the human postpartum uterus.

3. Ergotocin, unlike ergotoxine or ergotamine, has little inhibitory action on epinephrine.

4. Ergotocin in the form of a maleate was shown to have a minimal lethal dose of 250 mgm. per kilogram in mice by intravenous injection, and of 80 mgm. per kilogram in guinea pigs by the same route of administration. Death is preceded by clonic convulsions. Three out of 6 cocks injected intramuscularly with 1 mgm. daily developed gangrene of their comb. A transient albuminuria, which almost disappeared before the end of the experiment, was observed in a dog given intravenously 1 mgm. per kilogram per day.

5. Ergotocin causes mydriasis on instillation into the rabbit's eye, constriction of frog's limb vessels, and relaxation of isolated rabbit's small intestines; the latter effect can be abolished by the previous application of ergotamine. These results seem to indicate that the new ergot principle has a stimulating action on the sympathetic endings.

6. Ergotocin has sometimes a demonstrable pressor action in pithed cats, but a depressor action in anesthetized animals. In large doses, it suppresses the respiration. In white rats it increases the metabolic rate when injected intravenously in appropriate doses.