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BOR - Papers in Press, published online ahead of print August 16, 2006.
Biol Reprod 2006, 10.1095/biolreprod.106.053637
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BIOLOGY OF REPRODUCTION 75, 809–814 (2006)
DOI: 10.1095/biolreprod.106.053637
© 2006 by the Society for the Study of Reproduction, Inc.

Research Article

Barusiban, An Effective Long-Term Treatment of Oxytocin-Induced Preterm Labor in Nonhuman Primates1

Torsten M. Reinheimer 5, Gary J. Chellman 2 6, John C. Resendez 3 6, Julie K. Meyer 6, and Walter H. Bee 4 6

Ferring Pharmaceuticals A/S,5 International PharmaScience Center, Department of Non-Clinical Development, Copenhagen S, 2300 Denmark Charles River Laboratories Preclinical Services,6 Sparks, Nevada 89431

ABSTRACT

Preterm labor (PTL) affects up to 25% of human pregnancies in developing countries, but there are few therapeutic options. Based on the key role of oxytocin (OXT) in labor and parturition, OXT antagonists are a potentially useful class of drugs for PTL. Barusiban is a new selective, potent, and long-acting OXT receptor antagonist. In this study barusiban was given by continuous i.v. infusion to monkeys during the last 3 wk of pregnancy; the monkeys were also given daily doses of OXT to induce uterine contractions and simulate PTL. Barusiban effectively suppressed OXT-induced PTL-like contractions and prevented early delivery. In contrast, fenoterol (a beta2-adrenoceptor [beta2-AR] agonist used as a comparative control) did not inhibit uterine contractions in this model. Barusiban was particularly effective in maintaining low intrauterine pressure (IUP) near the end of pregnancy, which is when IUP in both OXT controls and fenoterol-treated females increased substantially. Although barusiban delayed the onset of labor, it did not prevent normal delivery. These data demonstrate the safety and efficacy of barusiban in reducing uterine contractility in response to repeated OXT challenge, and suggest that barusiban may be therapeutically effective in long-term treatment of PTL.

neuropeptides, parturition, pregnancy, oxytocin, uterus

FOOTNOTES

1 Presented in part at the 46th spring meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology, 15–17 March 2005, Mainz, Germany; and at the 52nd annual meeting of the Society for Gynecologic Investigation, 23–26 March 2005, Los Angeles, CA.

2 Correspondence: G.J. Chellman, Developmental and Reproductive Toxicology Program, Charles River Laboratories Preclinical Services, 587 Dunn Circle, Sparks, NV 89431. FAX: 775 331 2289; gary.chellman{at}us.crl.com

3 Current address: MPI Research, Inc., Mattawan, MI 49071.

4 Current address: Scios, Inc., Fremont, CA 94555.


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Biol Reprod 2006 75: 663. [Full Text]  





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Copyright © 2006 by the Society for the Study of Reproduction.