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Journal of the Society for Gynecologic Investigation
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Comparison of the In Vivo Activity of Different Oxytocin Antagonists in the Pregnant Baboon

Moshe D. Fejgin, MD

Sok Cheon Pak, PhD

George Flouret, PhD

Michael T. Parsons, MD

Department of Obstetrics and Gynecology, University of Illinois at Chicago, Chicago, Illinois; Department of Obstetrics and Gynecology, University of South Florida, Tampa, Florida; Department of Physiology, Northwestern University Medical School, Chicago, Illinois

Laird Wilson, Jr, PhD

Department of Obstetrics and Gynecology, University of Illinois at Chicago, Chicago, Illinois; Department of Obstetrics and Gynecology, University of South Florida, Tampa, Florida; Department of Physiology, Northwestern University Medical School, Chicago, Illinois; Department of Obstetrics and Gynecology, University of Illinois Medical Center (M/C 808), 820 South Wood Street, Chicago, IL 60612

Objective: To ascertain the relative activity of five oxytocin antagonists (OTAs) in vivo in a tethered pregnant baboon model and compare these results to previously reported affinities in human and rat oxytocin receptor assays and median effective dose in rat uterotonic bioassay.

Methods: Pregnant tethered baboons between days 130 and 160 of pregnancy were given an oxytocin challenge test 1 minute after infusion of 1 mg of one of five randomly selected OTAs: ANTAG I, ANTAG II, ANTAG III, L366948, and Atosiban. Once the uterine response to exytocin returned to normal (1-8 days) the OCT was repeated with one of the remaining, untested OTAs during the 130-160 day period. Uterine activity, the time until the first significant response, and the dose of oxytocin needed to induce this response were all factored into one expression, the antagonist-response interval (ARI).

Results: When expressed as ratio to ANTAG I the relative ARI for the OTAs were 0, .5, 1.0, 2.4 and 59.2 for L366948, Atosiban, ANTAG I, ANTAG II, and ANTAG III, respectively. ANTAG III and L366948 were significantly different from each other and the three other OTAs (P < .05). The log10 ARI for the 4 active OTAs when correlated with the log10 of the human and rat oxytocin receptor affinities and the rat uterotonic bioassay were all highly correlated (r = .99; P < .05).

Conclusion: ANTAG III is a potent, long-acting OTA in vivo in the pregnant baboon and has the potential as a tocolytic in humans.

Key Words: Oxytocin antagonists • pregnant baboon • oxytocin challenge test • tocolytic

Journal of the Society for Gynecologic Investigation, Vol. 5, No. 5, 251-254 (1998)
DOI: 10.1177/107155769800500505
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