7-Chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1 H -1-benzazepine (OPC-41061): A potent, orally active nonpeptide arginine vasopressin V 2 receptor antagonist

Kondo, Kazumi; Ogawa, Hidenori; Yamashita, Hiroshi; Miyamoto, Hisashi; Tanaka, Motoyasu; Nakaya, Kenji; Kitano, Kazuyoshi; Yamamura, Yoshitaka; Nakamura, Shigeki; Onogawa, Toshiyuki; Mori, Toyoki; Tominaga, Michiaki

doi:10.1016/s0968-0896(99)00101-7

Cited by 99 publications

(53 citation statements)

References 19 publications

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“…Tolvaptan is an orally active benzazepine derivative arginine vasopressin (AVP) V 2 -receptor antagonist [8]. Pharmacologically, tolvaptan inhibits AVP binding to V 2 -receptors in the distal portion of the nephron, thus inhibiting water reabsorption without an increase in urine electrolyte excretion, i.e.…”

Section: Introductionmentioning

confidence: 99%

Effects of Tolvaptan on Systemic and Renal Hemodynamic Function in Dogs with Congestive Heart Failure

Onogawa

Sakamoto

Nakamura

et al. 2011

Cardiovasc Drugs Ther

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Purpose We investigated the effects of tolvaptan, a vasopressin V 2 -receptor antagonist, on diuretic response and systemic and renal hemodynamic characteristics in conscious dogs with congestive heart failure (CHF). We also compared these effects with those of furosemide, a loop diuretic. Methods CHF was induced by rapid right-ventricular pacing at 260 beats/min for at least 3 weeks, and maintained with a pacing rate of 220-240 beats/min. CHF dogs were orally given tolvaptan (10 mg/kg), furosemide (10 mg/kg) and vehicle in random order during the stable CHF state. Urine excretion, systemic and renal hemodynamic parameters, and plasma hormone levels were measured over 6-hour periods after drug administration. Results Tolvaptan induced aquaresis with an increase in free water clearance, resulting in a significant increase in serum sodium concentrations and a decrease in cumulative water balance. Tolvaptan also decreased pulmonary capillary wedge pressure without affecting systemic vascular resistance, glomerular filtration rate or renal blood flow. Tolvaptan tended to increase plasma arginine vasopressin concentrations but did not affect plasma renin activity. In contrast, furosemide induced clear saluresis with increased electrolyte excretion, resulting in decreased pulmonary capillary wedge pressure. However, furosemide also decreased serum potassium concentration and increased plasma arginine vasopressin concentrations and plasma renin activity.Conclusion Tolvaptan elicited a potent aquaretic response and reduced the cardiac preload without unfavorable effects on systemic or renal hemodynamics, the renin-angiotensinaldosterone system, or the sympathetic nervous system in CHF dogs. Thus, tolvaptan may offer a novel approach to remove excess water congestion from patients with CHF.

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Section: Introductionmentioning

confidence: 99%

Effects of Tolvaptan on Systemic and Renal Hemodynamic Function in Dogs with Congestive Heart Failure

Onogawa

Sakamoto

Nakamura

et al. 2011

Cardiovasc Drugs Ther

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“…Tolvaptan, N-{4-[(5RS)-7-chloro-5-hydroxy-2,3,4,5-tetrahydro-1H-benzo[b]azepine-1-carbonyl]-3-methylphenyl}-2-methylbenzamide (Otsuka Pharmaceutical Co., Ltd), is a potent, highly selective, and orally effective nonpeptide V2 receptor antagonist [1]. It promotes aquaresis, leading to an increases in urine volume and electrolyte-free water clearance, and a decrease in urine osmolality [2,3].…”

Section: Introductionmentioning

confidence: 99%

Nonclinical Safety Profile of Tolvaptan

Morishita

Awogi

et al. 2011

Cardiovasc Drugs Ther

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“…Tolvaptan is a nonpeptide benzazepine derivative that acts as a potent AVP receptor antagonist [ 27 ]. Initial experimental in vitro and in vivo studies showed that tolvaptan inhibited cAMP production induced by AVP with no intrinsic agonist activity; it was 29 times more selective for V 2 than for V 1a receptors and produced a clear aquaretic effect after single and multiple oral dosing [ 28 ].…”

Section: Tolvaptanmentioning

confidence: 99%

Vasopressin and vasopressin antagonists in heart failure and hyponatremia

Farmakis¹,

Filippatos

Kremastinos³

et al. 2008

Curr Heart Fail Rep

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Increased synthesis of arginine vasopressin (AVP) plays a critical role in fluid retention and hyponatremia in patients with heart failure. The AVP receptor antagonists constitute a new class of agents that are promising in the management of hyponatremia and congestion. Three of these agents--conivaptan, tolvaptan, and lixivaptan--have been studied in clinical settings. All are effective in inducing aquaresis (ie, electrolyte-free water excretion) and normalizing serum sodium concentration. They are well tolerated without causing electrolyte disorders, hypotension, or renal impairment. Conivaptan has been approved by the US Food and Drug Administration for short-term intravenous treatment of euvolemic hyponatremia of variable etiology but has not been adequately studied in heart failure. The addition of tolvaptan to standard therapy in hospitalized patients with heart failure has led to symptomatic improvement and decreased body weight, but there is no long-term clinical benefit. Early data on lixivaptan in heart failure suggest a dose-dependent aquaresis effect, and larger studies are under way.

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7-Chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1 H -1-benzazepine (OPC-41061): A potent, orally active nonpeptide arginine vasopressin V 2 receptor antagonist

Cited by 99 publications

References 19 publications

Effects of Tolvaptan on Systemic and Renal Hemodynamic Function in Dogs with Congestive Heart Failure

Effects of Tolvaptan on Systemic and Renal Hemodynamic Function in Dogs with Congestive Heart Failure

Nonclinical Safety Profile of Tolvaptan

Vasopressin and vasopressin antagonists in heart failure and hyponatremia

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