Some Pharmacologic Studies on 1-L-Penicillamine-oxytocin and 1-Deaminopenicillamine-oxytocin: Two Potent Oxytocin Inhibitors1

Abstract

The 2 analogs were devoid of activities characteristic of oxytocin. They inhibited the uterotonic activity of oxytocin in both in vitro and in vivo rat preparations. When tested on the isolated rat uterus, marked inhibition of oxytocin could be produced by as little as a 2.5:1 molar ratio of the inhibitor to oxytocin. The average effective molar ratio for 50% inhibition was 8.5:1 when the doses of oxytocin were between 5 and 10 mU in a 10 ml organ bath. In in vivo rat preparations in which rhythmic contractions of the uterus were induced by a continuous infusion of oxytocin, effective doses of 1-L-penicillamine-oxytocin and 1-deaminopenicillamine-oxytocin produced partial to complete inhibition of uterine motility. The inhibition is competitive and reversible in nature. The inhibitory activity of these 2 analogs is very specific. They inhibited only the responses to oxytocin and its structural analogs. They had no inhibitory effect on the responses to angiotensin or bradykinin or on spontaneous uterine contractions. The specificity of the inhibitory activity of these 2 peptides provided many interesting data which have some bearing on the drug-receptor interaction theory and on the nature of the uterine receptor for oxytocin.