Effect of changing the COOH-terminal amide group present in the hydrophilic cluster of oxytocin to dimethylamide.
Oxytocinoic acid dimethylamide was synthesized by stepwise solution techniques as part of an ongoing evaluation of the effects on the biological activity of oxytocin caused by individually changing the groups that comprises the hydrophilic surface of the hormone to more hydrophobic and more bulky groups. The analogue exhibited approximately 3% of the potency of oxytocin in the in vitro uterotonic assay. In addition, it possesses potencies of less than 0.07, less than 0.01, and 0.096 unit/mg in the avian vasodepressor, rat pressor, and rat antidiuretic assays, respectively. In the in vitro uterotonic assay, oxytocinoic acid dimethylamide showed a reduced affinity for the oxytocin receptor, a nonparallel dose-response relationship, and most importantly a reduced intrinsic activity as compared to oxytocin. The results suggest that the replacement of the protons of the primary carboxyamide of Gly9-NH2 of oxytocin by methyl groups displaces the active elements from the orientation for obtaining maximal intrinsic activity in the isolated rat uterus.
D000818:Animals; D002645:Chickens; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008968:Molecular Conformation; D010120:Oxytocics / Q000138:chemical synthesis*; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D014590:Uterine Contraction / Q000187:drug effects
D010120:Oxytocics; D010121:Oxytocin; C025938:oxytocinoic acid dimethylamide