{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T17:18:26Z","timestamp":1793380706820,"version":"4.5.0"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T00:00:00Z","timestamp":1675900800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Contraction of the uterus is critical for parturient processes. Insufficient uterine tone, resulting in atony, can potentiate postpartum hemorrhage; thus, it is a major risk factor and is the main cause of maternity-related deaths worldwide. Oxytocin (OT) is recommended for use in combination with other uterotonics for cases of refractory uterine atony. However, as the effect of OT dose on uterine contraction and control of blood loss during cesarean delivery for labor arrest are highly associated with side effects, small amounts of uterotonics may be used to elicit rapid and superior uterine contraction. We have previously synthesized OT analogs 2 and 5, prolines at the 7<jats:sup>th<\/jats:sup> positions of which were replaced with N-(p-fluorobenzyl) glycine [thus, compound 2 is now called fluorobenzyl (FBOT)] or N-(3-hydroxypropyl) glycine [compound 5 is now called hydroxypropyl (HPOT)], which exhibited highly potent binding affinities for human OT receptors <jats:italic>in vitro<\/jats:italic>. In this study, we measured the <jats:italic>ex vivo<\/jats:italic> effects of FBOT and HPOT on contractions of uteri isolated from human cesarean delivery samples and virgin female mice. We evaluated the potency and efficacy of the analogs on uterine contraction, additivity with OT, and the ability to overcome the effects of atosiban, an OT antagonist. In human samples, the potency rank judged by the calculated EC<jats:sub>50<\/jats:sub> (pM) was as follows: HPOT (189) &gt; FBOT (556) &gt; OT (5,340) &gt; carbetocin (12,090). The calculated Emax was 86% for FBOT and 75% for HPOT (100%). Recovery from atosiban inhibition after HPOT treatment was as potent as that after OT treatment. HPOT showed additivity with OT. FBOT (56 pM) was found to be the strongest agonist in virgin mouse uterus. HPOT and FBOT demonstrated high potency and partial agonist efficacy in the human uterus. These results suggested that HPOT and FBOT are highly uterotonic for the human uterus and performed better than OT, indicating that they may prevent postpartum hemorrhage.<\/jats:p>","DOI":"10.1371\/journal.pone.0281363","type":"journal-article","created":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T18:46:08Z","timestamp":1675968368000},"page":"e0281363","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Two oxytocin analogs, N-(p-fluorobenzyl) glycine and N-(3-hydroxypropyl) glycine, induce uterine contractions ex vivo in ways that differ from that of oxytocin"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5093-3480","authenticated-orcid":true,"given":"Stanislav 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