Molecular Pharmacology, Vol 6, 474-480, Copyright © 1970 by the American Society for Pharmacology and Experimental Therapeutics

Crystalline Deamino-dicarba-oxytocin

Preparation and Some Pharmacological Properties

¹ Institute for Protein Research, Osaka University, Kita-ku, Osaka, Japan
² Department of Physiology, The Mount Sinai Medical and Graduate Schools, New York, New York 10029, and Medical Research Center, Brookhaven National Laboratory, Upton, New York 11973

Deamino-dicarba-oxytocin, a synthetic analogue of oxytocin in which both sulfur atoms are formally replaced by methylene moieties and the terminal amino group by a hydrogen atom, has been obtained as highly pure crystalline material. Upon bioassay this analogue exhibited 160 ± 4.4 units/mg of oxytocic activity, 44 ± 1.7 units/mg of avian vasodepressor activity, 140 ± 7 units/mg of rabbit milk-ejecting activity, 0.10 ± 0.02 unit/mg of rat pressor activity, and 4.7 ± 0.3 units/mg of rat antidiuretic activity.

Cumulative dose-response studies on the isolated rat uterus, mounted in magnesium-free van Dyke-Hastings solution, showed that the maximal attainable contractile response (intrinsic activity) of deamino-dicarba-oxytocin was only 68% of that of the natural oxytocic principle. Deamino-dicarba-oxytocin had a pD₂ value (the negative logarithm of the concentration of the analogue that will evoke a half-maximal effect) of 8.35 ± 0.07; the pD₂ value is a measure of time affinity of the analogue for its uterine receptor.

The presence of 0.5 mM Mg⁺⁺ in the ambient fluid potentiated time contractile capacity of the uterus in response to deamino-dicarba-oxytocin; the intrinsic activity was increased by 35% over its original value.

Solutions in deamino-dicarba-oxytocin were found to be resistant to inactivation during lyophilization from water (pH 6) or aqueous triethylamine (pH 9).

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ACKNOWLEDGMENTS We would like to thank Miss M. Wahrenburg and Mrs. I. Mintz for their highly skillful assistance in this study.