Reactome | AVPR1A,2 bind AVPR antagonists

AVPR1A,2 bind AVPR antagonists

Stable Identifier

R-HSA-9667569

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, extracellular region

ReviewStatus

5/5

Locations in the PathwayBrowser

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Signal Transduction (Homo sapiens)

- Signaling by GPCR (Homo sapiens)
  - GPCR ligand binding (Homo sapiens)
    - Class A/1 (Rhodopsin-like receptors) (Homo sapiens)
      - Peptide ligand-binding receptors (Homo sapiens)
        
        Vasopressin-like receptors (Homo sapiens)
        
        AVPR1A,2 bind AVPR antagonists (Homo sapiens)

General

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Conivaptan (YM087, brand name Vaprisol) (Tahara et al. 1998, 1998b) and tolvaptan (trade names Samsca, Jinarc) (Schrier et al. 2006) are non-peptide inhibitors of the vasopressin receptors AVPR1A and AVPR2. They are used to treat hyponatremia (low blood sodium levels) (Greenberg & Verbalis 2006). They function by antagonizing AVPR2 receptors in the renal collecting ducts thus causing aquaresis (water secretion) but without electrolyte loss. AVPV2 receptor antagonists may also be useful in the treatment of polycystic kidney disease (PKD) (Belibi et al. 2004, Poch et al. 2018). Satavaptan was under investigation in clinical trials for the prevention of ascites (Soupart et al. 2006) and hyponatremia (Gines et al. 2008) but development has been discontinued. Lixivaptan is a potent, non-peptide, selective AVPR2 antagonist (Albright et al. 1998) that shows promise in treating heart failure in patients with hyponatremia (Abraham et al. 2008, Liamis et al. 2014).

Literature References

PubMed ID	Title	Journal	Year
16672911	Vasopressin receptor antagonists Greenberg, A, Verbalis, JG	Kidney Int.	2006
30303493	An update on tolvaptan for autosomal dominant polycystic kidney disease Blasco, M, Rodas, L, Quintana, L, Poch, E, Molina, A	Drugs Today	2018
24766294	Treatment of hyponatremia: the role of lixivaptan Liamis, G, Elisaf, MS, Filippatos, TD		2014
17699341	Successful long-term treatment of hyponatremia in syndrome of inappropriate antidiuretic hormone secretion with satavaptan (SR121463B), an orally active nonpeptide vasopressin V2-receptor antagonist Legros, JJ, Alföldi, S, Soupart, A, Heshmati, HM, Annane, D, Gross, P, Decaux, G		2006
9884074	Pharmacological characterization of the human vasopressin receptor subtypes stably expressed in Chinese hamster ovary cells Wada, K, Ishii, N, Sugimoto, T, Tsukada, J, Saito, M, Tahara, A, Tomura, Y, Yatsu, T, Tanaka, A, Uchida, W, Kusayama, T	Br. J. Pharmacol.	1998
9651149	5-Fluoro-2-methyl-N-[4-(5H-pyrrolo[2,1-c]-[1, 4]benzodiazepin-10(11H)-ylcarbonyl)-3-chlorophenyl]benzamide (VPA-985): an orally active arginine vasopressin antagonist with selectivity for V2 receptors Reich, MF, Sum, FW, Mazandarani, H, Bailey, T, Albright, JD, Venkatesan, AM, Dusza, JP, Chan, PS, Coupet, J, Delos Santos, EG, Ru, X		1998
9459574	Pharmacological characterization of YM087, a potent, nonpeptide human vasopressin V1A and V2 receptor antagonist Wada, K, Ishii, N, Sugimoto, T, Tsukada, J, Saito, M, Tahara, A, Tomura, Y, Yatsu, T, Tanaka, A, Uchida, W, Kusayama, T	Naunyn Schmiedebergs Arch. Pharmacol.	1998
17105757	Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia Berl, T, Verbalis, JG, Schrier, RW, Czerwiec, FS, SALT Investigators, -, Orlandi, C, Gross, P, Gheorghiade, M	N. Engl. J. Med.	2006
20973922	Rationale and design of the treatment of hyponatremia based on lixivaptan in NYHA class III/IV cardiac patient evaluation (THE BALANCE) study Abraham, WT, Hasenfuss, G, Aranda, JM, Elkayam, U, Orlandi, C, Kukin, M, Gilbert, EM, Gottlieb, SS, Tavazzi, L, Feldman, AM, Lowes, BD, O'Connell, JB, Ticho, B, Boehmer, JP		2010
18508290	Effects of satavaptan, a selective vasopressin V(2) receptor antagonist, on ascites and serum sodium in cirrhosis with hyponatremia: a randomized trial Wong, F, Ginès, P, Milutinovic, S, Watson, H, HypoCAT Study Investigators, -, Olteanu, D, del Arbol, LR		2008
15327388	Cyclic AMP promotes growth and secretion in human polycystic kidney epithelial cells Helmkamp, GM, Grantham, JJ, Reif, G, Wallace, DP, Li, H, Yamaguchi, T, Belibi, FA, Olsen, L	Kidney Int.	2004