Reference

Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure

Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure. Gheorghiade, Mihai; Niazi, Imran; Ouyang, John; Czerwiec, Frank; Kambayashi, Jun-Ichi; Zampino, Manuela; Orlandi, Cesare (Feinberg School of Medicine, Northwestern University, Chicago, IL, USA). Circulation, 107(21), 2690-2696 (English) 2003 Lippincott Williams & Wilkins. CODEN: CIRCAZ. ISSN: 0009-7322. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) In this study, we evaluated the effects of tolvaptan (OPC-41061), a novel, oral, nonpeptide vasopressin V2-receptor antagonist in patients with chronic heart failure (CHF). This was a double-blind study investigating the effects of three doses of tolvaptan and placebo in patients with CHF. After a run-in period, 254 patients were randomly assigned to placebo (n=63) or tolvaptan [30 mg (n=64), 45 mg (n=64), or 60 mg (n=63)] once daily for 25 days. Patients were not fluid-restricted and were maintained on stable doses of furosemide. At day 1, when compared with baseline, a decrease in body wt. of -0.79±0.99, -0.96±0.93, and -0.84±0.02 kg was obsd. in the 30-, 45-, and 60-mg tolvaptan groups, resp., and a body wt. increase of +0.32±0.46 kg in the placebo group (P<0.001 for all treatment groups vs. placebo). Although the initial decrease in body wt. was maintained during the study, no further redn. was obsd. beyond the first day. An increase in urine vol. was obsd. with tolvaptan when compared with placebo (3.9±0.6, 4.2±0.9, 4.6±0.4, and 2.3±0.2 L/24 h at day 1 for 30-, 45-, and 60-mg tolvaptan groups, and placebo, resp.; P<0.001). A decrease in edema and a normalization of serum sodium in patients with hyponatremia were obsd. in the tolvaptan group but not in the placebo group. 150683-30-0 and 7440-23-5 are just another two chemicals used in this study. No significant changes in heart rate, blood pressure, serum potassium, or renal function were obsd. In patients with CHF, tolvaptan was well tolerated; it reduced body wt. and edema and normalized serum sodium in the hyponatremic patients. .

Tolvaptan in treatment of heart failure: vasopressin V2 antagonist

Tolvaptan in treatment of heart failure: vasopressin V2 antagonist. Sorbera, L. A.; Castaner, J.; Bayes, M. 150683-30-0 and 113-79-1 are cas registry numbers. These chemicals are also mentioned in this article.; Silvestre, J. (Prous Science, Barcelona 08080, Spain). Drugs of the Future, 27(4), 350-357 (English) 2002 Prous Science. CODEN: DRFUD4. ISSN: 0377-8282. DOCUMENT TYPE: Journal; General Review CA Section: 1 (Pharmacology) A review. Congestive heart failure is a condition in which impaired cardiac function causes circulatory congestion. Although there is no cure, several classes of agents are available or under development to improve cardiac function, relieve symptoms and improve quality of life of patients. Arginine vasopressin (AVP) is a potent antidiuretic hormone that plays a crucial role in the regulation of free water absorption, body fluid osmolality, blood vol., cell contraction and blood pressure and its diverse actions are mediated by the G-protein-coupled receptor subtypes V1, V2 and V3. The systemic vasoconstriction and dilutional hyponatremia seen in patients with congestive heart failure are due, in part, to abnormally high levels of circulating AVP. AVP antagonism is therefore a feasible strategy to prevent disease progression in heart failure. The orally active benzazepine tolvaptan (OPC-41061) is a V2 receptor antagonist that has demonstrated excellent preclin. and clin. aquaretic effects indicating its potential efficacy in the treatment of hyponatremia seen in congestive heart failure as well as other conditions such as liver cirrhosis and renal pathologies. .