TY - JOUR T1 - Pharmacological Profile of YM087, A Novel Potent Nonpeptide Vasopressin V<sub>1A</sub> and V<sub>2</sub> Receptor Antagonist,<em>in Vitro</em> and <em>in Vivo</em> JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 301 LP - 308 VL - 282 IS - 1 AU - Atsuo Tahara AU - Yuichi Tomura AU - Koh-Ichi Wada AU - Toshiyuki Kusayama AU - Junko Tsukada AU - Masahiro Takanashi AU - Takeyuki Yatsu AU - Wataru Uchida AU - Akihiro Tanaka Y1 - 1997/07/01 UR - http://jpet.aspetjournals.org/content/282/1/301.abstract N2 - The biochemical and pharmacological profile of YM087, 4′-[(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepin-6-yl)-carbonyl]-2-phenylbenzanilide monohydrochloride, a newly synthesized nonpeptide vasopressin (AVP) antagonist, was investigated in several in vitro andin vivo studies. YM087 showed high affinity for V1A receptors from rat liver and V2 receptors from rat kidney with Ki values of 0.48 and 3.04 nM, respectively. YM087 also inhibited [3H]oxytocin (OT) binding to rat uterus (OT receptors) plasma membranes with aKi value of 44.4 nM, and at 100 μM did not affect the binding of [3H]AVP to anterior pituitary (V1B receptors) plasma membranes, which indicated that it had less affinity for these OT and V1B receptors. YM087 had no effect on cytosolic free calcium concentration ([Ca++]i) itself, but suppressed AVP-induced increase in [Ca++]i of cultured vascular smooth muscle cells at the same concentrations as the binding affinities. Furthermore, YM087 potently blocked AVP-induced cAMP production of cultured renal epithelium cells concentration dependently and had no agonistic activities. In in vivo studies, intravenous administration of YM087 inhibited the pressor response to exogenous AVP in pithed rats and produced an aquaretic effect in dehydrated conscious rats in a dose-dependent manner. These results demonstrate that YM087 is a potent and nonpeptide dual AVP V1A and V2 receptors antagonist and can be used in future studies to help clarify the physiological and pathophysiological roles of AVP. The American Society for Pharmacology and Experimental Therapeutics ER -