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Tolvaptan antagonists

Inhibition of V2 vasopressin receptors causes an increase in urine volume primarily by reducing the re-absoiption of water along the collecting duct, an aquaretic effect that is fundamentally different from the natriuretic actions discussed so far. Nevertheless, some of the conditions calling for the use of natriuretic intervention are identical to those in which the administration of a new class of orally active nonpeptide V2 antagonists may be useful (tolvaptan, lixivaptan, and others). [Pg.431]

Several selective V2R antagonists have also been developed (tolvaptan, lixivaptan, OPC-31260, Satavaptan, RWJ-351647). These substances, together with conivaptan, are also known as aquaretic agents . [Pg.1277]

Catalytic reduction of the nitro group proceeds to the aniline (4-9). The chain is next extended by acylation of the newly formed amine with ortho-toluyl chloride (4-10) to give (4-11). Reduction of the azepinone carbonyl group with borohydride affords the vasopressin antagonist tolvaptan (4-12) [5]. [Pg.499]

Antidiuretic hormone antagonists are used to manage SIADH when water restriction has failed to correct the abnormality. This generally occurs in the outpatient setting, where water restriction cannot be enforced, or in the hospital when large quantities of intravenous fluid are needed for other purposes. Lithium carbonate has been used to treat this syndrome, but the response is unpredictable. Demeclocycline, in dosages of 600-1200 mg/d, yields a more predictable result and is less toxic. Appropriate plasma levels (2 mcg/mL) should be maintained by monitoring. Unlike demeclocycline, conivaptan is administered by IV injection, so it is not suitable for chronic use in outpatients. Lixivaptan and tolvaptan should soon be available for oral use. [Pg.337]

A group of nonpeptide antagonists of vasopressin receptors is being investigated for use in patients with hyponatremia or acute heart failure, which is often associated with elevated concentrations of vasopressin. Conivaptan has high affinity for both Vla and V2 receptors. Tolvaptan has a 30-fold higher affinity for V2 than for Vi receptors. In several clinical trials,... [Pg.845]

Vasopressin receptor antagonists, such as relcovaptan (an antagonist at Vla receptors), lixivaptan and tolvaptan (V2), and conivaptan (mixed V a/V2), are also under development (1). [Pg.521]

Schrier RW, Gross P, Gheorghiade M, Berl T, Verbalis JG, Czerwiec FS, Orlandi C SALT Investigators. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med 2006 355(20) 2099-112. [Pg.525]

Shoaf SE, Wang Z, Bricmont P, Mallikaarjun S. Pharmacokinetics, pharmacodynamics, and safety of tolvaptan, a nonpeptide AVP antagonist, during ascending singledose studies in healthy subjects. J Clin Pharmacol 2007 47(12) 1498-507. [Pg.525]

Shoaf SE, Bramer SL, Bricmont P, Zimmer CA. Pharmacokinetic and pharmacodynamic interaction between tolvaptan, a non-peptide AVP antagonist, and fur-osemide or hydrochlorothiazide. J Cardiovasc Pharmacol 2007 50(2) 213-22. [Pg.525]

As Of 2009, conivaptan HCl (1) is one of three vasopressin receptor antagonists approved for use in the treatment of hyponatremia worldwide. The U.S. approval of 1 was preceded by the 2006 approval of mozavaptan hydrochloride (2) in Japan. In 2009, tolvaptan (3) joined 1 as an FDA-approved agent for the treatment of hyponatremia. In this chapter, the pharmacological profile and synthesis of conivaptan hydrochloride (1) is examined in detail. [Pg.176]

In CHO cells transfected with human V], and V2 vasopressin receptors, 1 inhibits [3H]-AVP binding with K/s of 4.3 and 1.9 nM, respectively.15 Compound 1 demonstrates similar activity on rat Vla and V2 receptors, with Kj s of 0.48 nM and 3.0 nM (Table 1). As a result of significant structural homology between the vasopressin and the oxytocin receptors, 1 and AVP also demonstrate significant oxytocin receptor affinities (rat receptor Kt s of 44.4 nM and 3.4 nM, respectively).16 As seen in Table 1, the balanced binding affinities of 1 toward rat Via and V2 receptors closely parallel those of AVP in contrast, vasopressin receptor antagonists mozavaptan hydrochloride (2) and tolvaptan (3) demonstrate moderate to significant V2 receptor selectivity. [Pg.178]

Cardenas A, Gines P, Marotta P, Czerwiec F, Oyuang J, Guevara M, et al. Tolvaptan, an oral vasopressin antagonist, in the treatment of hyponatremia in cirrhosis. J Hepatol 2012 56(3) 571-8. [Pg.674]


See other pages where Tolvaptan antagonists is mentioned: [Pg.1278]    [Pg.59]    [Pg.474]    [Pg.529]    [Pg.337]    [Pg.189]    [Pg.1278]    [Pg.186]    [Pg.226]    [Pg.510]    [Pg.915]   


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Tolvaptan

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