Advances in the design of selective antagonists, potential tocolytics, and radioiodinated ligands for oxytocin receptors.
Despite intensive efforts over three decades in many laboratories, attempts to design peptide antagonists of oxytocin (OT) which are more selective for OT uterine receptors than for vasopressin (AVP), vasopressor V1a receptors, have met with only limited success. We will review the current status of the field and report on studies in our laboratories which have led to the design of highly potent non-selective and selective OT antagonists. Virtually all are more potent (2-6 fold) and a number are more selective (10-12 fold) than Atosiban, currently in clinical trial as a tocolytic agent. Many of these new published and unpublished OT antagonists are thus promising candidates for development as potential tocolytic agents for the prevention of pre-term labor. We also report on promising new radioiodinatable ligands for OT receptors. All the new OT antagonists are valuable new tools for studies on the physiological roles of OT and as probes for OT and AVP receptors.
Manning
M
M
Department of Biochemistry and Molecular Biology, Medical College of Ohio, Toledo, USA.
Cheng
L L
LL
Klis
W A
WA
Stoev
S
S
Przybylski
J
J
Bankowski
K
K
Sawyer
W H
WH
Barberis
C
C
Chan
W Y
WY
D000595:Amino Acid Sequence; D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000737:chemistry; D015195:Drug Design; D005260:Female; D006727:Hormone Antagonists / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D007457:Iodine Radioisotopes; D008024:Ligands; D008969:Molecular Sequence Data; D010121:Oxytocin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000737:chemistry; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015149:Tocolytic Agents / Q000737:chemistry; D014599:Uterus / Q000378:metabolism; D014668:Vasotocin / Q000031:analogs & derivatives / Q000737:chemistry
D006727:Hormone Antagonists; D007457:Iodine Radioisotopes; D008024:Ligands; D018045:Receptors, Oxytocin; D015149:Tocolytic Agents; D001127:Arginine Vasopressin; D010121:Oxytocin; D014668:Vasotocin