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.
Austin 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
Issue Date: 17-Sep-1999
Publication information: 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][1]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.
Gov't Doc #: 10528130
Type: Journal Article
Subjects: Administration, Oral
Antidiuretic Hormone Receptor Antagonists
Binding, Competitive.drug effects
Blood Pressure.drug effects
Dose-Response Relationship, Drug
Iodine Radioisotopes.diagnostic use
Kidney.drug effects.metabolism
Liver.drug effects.metabolism
Membranes.drug effects.metabolism
Radioligand Assay
Rats, Sprague-Dawley
Urination.drug effects
Appears in Collections:Journal articles

Show full item record

Page view(s)

checked on Nov 25, 2022

Google ScholarTM


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.