A nonpeptide oxytocin receptor antagonist radioligand highly selective for human receptors.
A novel, potent nonpeptide oxytocin receptor antagonist (1-(1-(2-(2,2,2-trifluoroethoxy)-4-(1-methylsulfonyl-4-piperidinyloxy) phenylacetyl)-4-piperidinyl)-3,4-dihydro-2(1H)-quinolinone) has been identified that can be labeled to high specific activity with [35S]. In binding studies, this compound exhibits sub-nanomolar affinity and a high degree of selectivity (900-1800-fold) for human oxytocin receptors compared to human vasopressin receptors. This compound appears suitable for studying the pharmacology of oxytocin receptors in human and nonhuman primate tissues, for which there is currently a paucity of highly selective tools. It may also be useful as a nonlabeled competitor or as a radioligand in autoradiographic studies of oxytocin receptor localization in these tissues.
Lemaire
Wei
W
Department of Neuroscience, Merck Research Laboratories, West Point, PA 19486, USA.
O'Brien
Julie A
JA
Burno
Maryann
M
Chaudhary
Ashok G
AG
Dean
Dennis C
DC
Williams
Peter D
PD
Freidinger
Roger M
RM
Pettibone
Douglas J
DJ
Williams
David L
DL
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001665:Binding Sites; D001667:Binding, Competitive; D001792:Blood Platelets / Q000378:metabolism; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D006224:Cricetinae; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D010880:Piperidines / Q000138:chemical synthesis / Q000494:pharmacology*; D015363:Quinolones / Q000138:chemical synthesis / Q000494:pharmacology*; D011869:Radioligand Assay; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D017483:Receptors, Vasopressin / Q000378:metabolism*
C472585:1-(1-(2-(2,2,2-trifluoroethoxy)-4-(1-methylsulfonyl-4-piperidinyloxy) phenylacetyl)-4-piperidinyl)-3,4-dihydro-2(1H)-quinolinone; D065092:Antidiuretic Hormone Receptor Antagonists; D008024:Ligands; D010880:Piperidines; D015363:Quinolones; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D002118:Calcium