Background:

Conivaptan (hydrochloride) is a non-peptide antagonist of vasopressin receptor, with Ki values of 0.48 and 3.04 nM for rat liver V1A receptor and rat kidney V2 receptor respectively.

Conivaptan (0.03, 0.1 and 0.3 mg/kg, i.v.) dose-dependently increases urine volume and reduces urine osmolality in both myocardial infarction and sham-operated rats. Conivaptan (0.3 mg/kg i.v.) significantly reduces right ventricular systolic pressure, left ventricular end-diastolic pressure, lung/body weight and right atrial pressure in myocardial infarction rats. Conivaptan (0.3 mg/kg i.v.) significantly increases dP/dt(max)/left ventricular pressure in myocardial infarction rats[1]. Conivaptan produces an acute increase in urine volume (UV), a reduction in osmolality (UOsm) and, at the end of the investigation, cirrhotic rats receiving the V(1a)/V(2)-AVP receptor antagonist does not show hyponatremia or hypoosmolality. Conivaptan also normalizes U(Na)V without affecting creatinine clearance and arterial pressure[2]. Conivaptan (0.01 to 0.1 mg/kg, i.v.) exerts a dose-dependent diuretic effect in dogs without an increase in the urinary excretion of electrolytes, inhibits the pressor effect of exogenous vasopressin in a dose-dependent manner (0.003 to 0.1 mg/kg i.v.) and, at the highest dose (0.1 mg/kg i.v.), almost completely blocks vasoconstriction caused by exogenous vasopressin. Conivaptan (0.1 mg/kg, i.v.) improves cardiac function, as evidenced by significant increases in left ventricular dP/dtmax, cardiac output and stroke volume, and reduces preload and afterload, as evidenced by significant decreases in left ventricular end-diastolic pressure and total peripheral vascular resistance in dogs with congestive heart failure[3].

参考文献:
[1]. Wada K, et al. Intravenous administration of conivaptan hydrochloride improves cardiac hemodynamics in rats with myocardial infarction-induced congestive heart failure. Eur J Pharmacol. 2005 Jan 10;507(1-3):145-51. Epub 2005 Jan 1.
[2]. Fernandez-Varo G, et al. Effect of the V1a/V2-AVP receptor antagonist, Conivaptan, on renal water metabolism and systemic hemodynamics in rats with cirrhosis and ascites. J Hepatol. 2003 Jun;38(6):755-61.
[3]. Yatsu T, et al. Cardiovascular and renal effects of conivaptan hydrochloride (YM087), a vasopressin V1A and V2 receptor antagonist, in dogs with pacing-induced congestive heart failure. Eur J Pharmacol. 1999 Jul 9;376(3):239-46.