Some biological properties of an "irreversible" antagonist of neurohypophyseal hormones, deamino-[Phe(4-BrCH2CONH)2]-oxytocin, and its isosteric analogue, deamino-[Phe(4-CH3CH2CONH)2]-oxytocin.
The 2-p-bromoacetylaminophenylalanine analogue of deamino-oxytoxin displayed some features of an irreversible inhibitor of oxytocin on rat uterus (long persistence of inhibitory effect, slow wash-out from the tissue). An isosteric analogue with a propionylamino group at the same position was, under similar experimental conditions, also an antagonist of oxytocin, but the features of an irreversible inhibitor were lacking. pA2 values of the two substances are between 6.5 and 6.9. The "irreversibility" of the former compound is concentration dependent and it is concluded that it cannot be entirely caused by a covalent binding of the inhibitor to the uterus receptor for oxytoxin. Like many other similar inhibitors, the substances display only an inefficient in vivo inhibition of the vasopressor effect of lysine vasopressin in rats.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D008236:Lypressin / Q000037:antagonists & inhibitors; D008297:Male; D008954:Models, Biological; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010909:Pituitary Hormones, Posterior / Q000037:antagonists & inhibitors*; D051381:Rats; D014590:Uterine Contraction / Q000187:drug effects
D010909:Pituitary Hormones, Posterior; D010121:Oxytocin; D008236:Lypressin