Studies on pharmacological and biochemical properties of deamino-dicarba-[GLY-7]-oxytocin  (Y-5350).
Pharmacological and biochemical properties were investigated on deamino-dicarba-[Gly-7]-oxytocin (Y-5350). This is a newly developed compound, in which the disulfide bond and [Pro-7] 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, adepressor activity was also evident in rats. In particular, the diuration 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 2mM 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 prescence 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.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002645:Chickens; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007774:Lactation / Q000187:drug effects; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008321:Mammary Glands, Animal / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000494:pharmacology; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D014590:Uterine Contraction / Q000187:drug effects; D014621:Vagina / Q000187:drug effects
D004791:Enzyme Inhibitors; C010483:deaminodicarba-Gly-oxytocin; D010121:Oxytocin; D008274:Magnesium