Crystalline deamino-dicarba-oxytocin. Preparation and some pharmacological properties.

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).