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Design of Oxytocin Analogs

Kazimierz Wiśniewski1

  • 1Ferring Research Institute Inc., San Diego, CA, USA. kazimierz.wisniewski@ferring.com.

Methods in Molecular Biology (Clifton, N.J.)
|May 29, 2019
PubMed

Insights

Oxytocin (OT) research spans decades, leading to analogs like atosiban and carbetocin for labor and hemorrhage. New analogs are being explored for central nervous system (CNS) diseases.

Area of Science:

  • Endocrinology
  • Neuroscience
  • Medicinal Chemistry

Background:

  • Oxytocin (OT) is a neurohypophyseal hormone with established uses in obstetrics.
  • Despite poor drug-like properties, OT is vital for labor induction, postpartum hemorrhage, and lactation support.
  • Recent interest explores OT's potential in treating central nervous system (CNS) diseases.

Purpose of the Study:

  • To review modifications of the oxytocin molecule.
  • To highlight the discovery of OT analogs with antagonistic and agonistic properties.
  • To discuss OT analogs developed for improved pharmacological profiles.

Main Methods:

  • Synthesis and biological evaluation of thousands of peptidic OT analogs since 1953.
  • Identification of mixed oxytocin receptor (OTR)/vasopressin 1a receptor (V1aR) antagonists (e.g., atosiban).
  • Development of longer-acting OTR agonists (e.g., carbetocin) and other improved analogs (e.g., barusiban).

Main Results:

  • Discovery of numerous OT analogs with diverse pharmacological properties.
  • Atosiban approved as a tocolytic agent in some countries.
  • Carbetocin is marketed for postpartum hemorrhage treatment.

Conclusions:

  • Extensive research has yielded OT analogs with enhanced properties.
  • These analogs serve as valuable therapeutic agents and pharmacological tools.
  • Ongoing research continues to explore OT analogs for CNS applications.
Keywords:
Clinical useDuration of actionOTR agonistsOTR antagonistsOxytocin (OT)Oxytocin receptor (OTR)Selectivity

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