Synthesis and some pharmacological properties of [4-threonine,7-sarcosine]oxytocin, a peptide with high oxytocic potency, and of [4-threonine,7-N-methylalanine]oxytocin.
Two analogues of oxytocin, [Thr4,Sar7]- and [Thr4,MeAla7]oxytocin, were synthesized and their pharmacological properties investigated. [Thr4,Sar7]oxytocin was found to exhibit high biological activity (uterotonic activity of 1174 +/- 104 and milk ejection activity of 731 +/- 57 units/mg) and high selectivity for oxytocin-like relative to vasopressin-like activities (antidiuretic activity of 0.037 +/- 0.012 unit/mg, undetectable pressor activity). [Thr4,MeAla7]oxytocin was characterized by markedly lower biological activities. In both analogues, the additivity of the effects of the residues in positions 4 and 7 of oxytocin on the biological activity of the analogues was ascertained.
D000818:Animals; D004231:Diuresis / Q000187:drug effects; D005260:Female; D007774:Lactation / Q000187:drug effects; D010120:Oxytocics / Q000138:chemical synthesis* / Q000494:pharmacology; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D014599:Uterus / Q000187:drug effects
D010120:Oxytocics; C039842:oxytocin, Thr(4)-Sar(7)-; D010121:Oxytocin; C039843:oxytocin, Thr(4)-N-MeAla(7)-