STUDIES ON PHARMACOLOGICAL AND BIOCHEMICAL PROPERTIES OF DEAMINO-DICARBA-[GLY7]-OXYTOCIN (Y-5350)

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Pharmacological and biochemical properties were investigated on deanmino-dicarba-[Gly7]-oxytocin (Y-5350). This is a newly developed compound, in which the disulfide bond and [Pro7] of deamino-oxytocin are substituted by an ethylene linkage and glycine respectively. Bioassayed Y-5350 exhibited 202.6 u/mg of oxytocic activity, 4.6 u/mg of avian depressor activity, 441.2 u/mg of rat milk-ejecting activity and 0.02 u/mg of rat antidiuretic activity, however, a depressor activity was also evident in rats. In particular, the duration of antidiuretic activity was short. Moreover, the oxytocic activity in pregnant rats and rabbits was weak in comparison with oxytocin. Cumulative dose-response studies were carried out on the isolated rat uterus using van Dyke-Hasting solution. The intrinsic activity was the same level as that of oxytocin, and the pD2 value was 8.62. Oxytocic activity was much enhanced by the existence of 0.5 or 2 mM magnesium ion in vitro. However, the agreement between in vivo and in vitro oxytocic activity was not complete when assay was carried out in the presence of 2 mM magnesium ion. Oxytocin was inactivated by the serum of pregnant women. In the experiment using rats, oxytocin was also destroyed by the extracts of uterus, kidney and liver. In contrast, Y-5350 was not destroyed by any of the enzyme solutions mentioned above.
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