Please use this identifier to cite or link to this item:
|Title:||In vivo and in vitro characterisation of a nonpeptide vasopressin V(1A) and V(2) receptor antagonist (YM087) in the rat.|
|Authors:||Risvanis, John;Naitoh, M;Johnston, Colin I;Burrell, Louise M|
|Affiliation:||Department of Medicine, The University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg, Victoria 3084, Australia.|
|Citation:||European Journal of Pharmacology; 381(1): 23-30|
|Abstract:||This paper reports the in vitro and in vivo characterisation of a nonpeptide, orally active, vasopressin V(1A) and V(2) receptor antagonist, YM087 (methyl-1,4,5,6-tetrahydroimidazo[4, 5-d]benzoazepine-6-carbonyl)-2-phenylbenzanilide monohydrochloride) in the rat. YM087 dose dependently displaced the vasopressin V(1A) receptor antagonist radioligand, 125I-labelled [d(CH(2))(5),sarcosine(7)]vasopressin at vasopressin V(1A) receptors in liver and kidney medulla membranes and caused a concentration dependent displacement of the vasopressin V(2) receptor antagonist radioligand [3H]desGly-NH(2)(9)[d(CH(2))(5), D-Ile(2), Ile(4)]vasopressin at vasopressin V(2) receptors in kidney medulla membranes. In vitro binding kinetic studies showed YM087 acted as a competitive antagonist at liver V(1A) and kidney V(1A) and V(2) vasopressin receptors. Oral administration of YM087 (0.1-3 mg/kg) dose dependently inhibited vasopressin binding to liver V(1A) and kidney V(1A) and V(2) vasopressin receptors over 24 h. Oral YM087 (1-3 mg/kg/day) for 7 days in normotensive rats caused a dose dependent aquaresis with no effect on systolic blood pressure. These results show that YM087 is an orally effective vasopressin V(1A) and V(2) receptor antagonist that may be useful in the treatment of conditions characterised by vasoconstriction and fluid retention such as congestive heart failure.|
|Internal ID Number:||10528130|
Antidiuretic Hormone Receptor Antagonists
Binding, Competitive.drug effects
Blood Pressure.drug effects
Dose-Response Relationship, Drug
Iodine Radioisotopes.diagnostic use
|Appears in Collections:||Journal articles|
Files in This Item:
There are no files associated with this item.
Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.