Conivaptan: a dual vasopressin receptor v1a/v2 antagonist [corrected].

Article Details

Citation

Copy to clipboard

Ali F, Raufi MA, Washington B, Ghali JK

Conivaptan: a dual vasopressin receptor v1a/v2 antagonist [corrected].

Cardiovasc Drug Rev. 2007 Fall;25(3):261-79.

PubMed ID

17919259 [ View in PubMed

]

Abstract

Several fluid retentive states such as heart failure, cirrhosis of the liver, and syndrome of inappropriate antidiuretic hormone secretion are associated with inappropriate elevation in plasma levels of arginine vasopressin (AVP), a neuropeptide that is secreted by the hypothalamus and plays a critical role in the regulation of serum osmolality and in circulatory homeostasis. The actions of AVP are mediated by three receptor subtypes V1a, V2, and V1b. The V1a receptor regulates vasodilation and cellular hypertrophy while the V2 receptor regulates free water excretion. The V1b receptor regulates adrenocorticotropin hormone release. Conivaptan is a nonpeptide dual V1a/V2 AVP receptor antagonist. It binds with high affinity, competitively, and reversibly to the V1a/V2 receptor subtypes; its antagonistic effect is concentration dependent. It inhibits CYP3A4 liver enzyme and elevates plasma levels of other drugs metabolized by this enzyme. It is approved only for short-term intravenous use. Infusion site reaction is the most common reason for discontinuation of the drug. In animals conivaptan increased urine volume and free water clearance. In heart failure models it improved hemodynamic parameters and free water excretion. Conivaptan has been shown to correct hyponatremia in euvolemic or hypervolemic patients. Its efficacy and safety for short-term use have led to the Food and Drug Administration (FDA) approval of its intravenous form for the correction of hyponatremia in euvolemic and hypervolemic states. Despite its ability to block the action of AVP on V1a receptors, no demonstrable benefit from this action was noted in patients with chronic compensated heart failure and it is not approved for this indication. Consideration should be given to further evaluation of its potential benefits in patients with acute decompensated heart failure.

DrugBank Data that Cites this Article

Drugs

Conivaptan

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Conivaptan	Vasopressin V1a receptor	Protein	Humans	Yes	Antagonist	Details
Conivaptan	Vasopressin V2 receptor	Protein	Humans	Yes	Antagonist	Details

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Conivaptan	Cytochrome P450 3A4	Protein	Humans	Unknown	Substrate Inhibitor	Details