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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:07:50
Primary Accession Number DB00872
Secondary Accession Number
  • APRD01302
Name Conivaptan
Drug Type
  • Approved
  • Investigational
  • Small Molecule
Description Conivaptan is a non-peptide inhibitor of antidiuretic hormone (vasopressin). It was approved in 2004 for hyponatremia (low blood sodium levels) caused by syndrome of inappropriate antidiuretic hormone (SIADH). Conivaptan inhibits both isotypes of the vasopressin receptor (V1a and V2).
Synonyms
  1. Conivaptan hydrochloride
  2. YM 087
  3. YM-087
  4. conivaptan
Brand Names
  1. Vaprisol
Brand Mixtures Not Available
Chemical IUPAC Name N-[4-(2-methyl4,5-dihydro-3H-imidazo[5,4-d][1]benzazepine-6-carbonyl)phenyl]-2-phenylbenzamide
Chemical Formula C32H26N4O2
Chemical Structure Structure
CAS Registry Number 210101-16-9
InChI Identifier InChI=1/C32H26N4O2/c1-21-33-28-19-20-36(29-14-8-7-13-27(29)30(28)34-21)32(38)23-15-17-24(18-16-23)35-31(37)26-12-6-5-11-25(26)22-9-3-2-4-10-22/h2-18H,19-20H2,1H3,(H,33,34)(H,35,37)/f/h33,35H
InChI Key IKENVDNFQMCRTR-BEFZCSJLCM
KEGG Drug D01236 Link Image
KEGG Compound Not Available
PubChem Compound 151171 Link Image
PubChem Substance 728713 Link Image
ChEBI ID Not Available
PharmGKB ID Not Available
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] Not Available
RxList Link Not Available
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Conivaptan Link Image
FDA Label
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Not Available
Average Molecular Weight 498.5744
Monoisotopic Molecular Weight 498.2056
State Solid
Melting Point Not Available
Experimental Water Solubility Very slightly soluble (0.15 mg/mL at 23oC) Source: PhysProp
Predicted Water Solubility 1.75e-03 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 6.3 Source: PhysProp
Predicted LogP 5.24 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -5.46 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES CC1=NC2=C(CCN(C(=O)C3=CC=C(NC(=O)C4=CC=CC=C4C4=CC=CC=C4)C=C3)C3=CC=CC=C23)N1
Canonical SMILES CC1=NC2=C(CCN(C(=O)C3=CC=C(NC(=O)C4=CC=CC=C4C4=CC=CC=C4)C=C3)C3=CC=CC=C23)N1
Drug Category
  • Aquaresis promoters
ATC Codes Not Available
AHFS Codes Not Available
Indication For the treatment of euvolemic hyponatremia (e.g. the syndrome of inappropriate secretion of antidiuretic hormone, or in the setting of hypothyroidism, adrenal insufficiency, pulmonary disorders, etc.) in hospitalized patients.
Pharmacology Conivaptan is a nonpeptide, dual antagonist of arginine vasopressin (AVP) V1A and V2 receptors. The level of AVP in circulating blood is critical for the regulation of water and electrolyte balance and is usually elevated in both euvolemic and hypervolemic hyponatremia. The AVP effect is mediated through V2 receptors, which are functionally coupled to aquaporin channels in the apical membrane of the collecting ducts of the kidney. These receptors help to maintain plasma osmolality within the normal range. The predominant pharmacodynamic effect of conivaptan in the treatment of hyponatremia is through its V2 antagonism of AVP in the renal collecting ducts, an effect that results in aquaresis, or excretion of free water. The pharmacodynamic effects of conivaptan include increased free water excretion (i.e., effective water clearance [EWC]) generally accompanied by increased net fluid loss, increased urine output, and decreased urine osmolality.
Mechanism of Action Conivaptan is a dual AVP antagonist with nanomolar affinity for human V1A and V2 receptors in vitro. This antagonism occurs in the renal collecting ducts, resulting in aquaresis, or excretion of free water.
Absorption Not Available
Toxicity Although no data on overdosage in humans are available, conivaptan has been administered as a 20 mg loading dose on Day 1 followed by continuous infusion of 80 mg/day for 4 days in hyponatremia patients and up to 120 mg/day for 2 days in CHF patients. No new toxicities were identified at these higher doses, but adverse events related to the pharmacologic activity of conivaptan, e.g. hypotension and thirst, occurred more frequently at these higher doses.
Protein Binding 99%
Biotransformation CYP3A4 is the sole cytochrome P450 isozyme responsible for the metabolism of conivaptan. Four metabolites have been identified. The pharmacological activity of the metabolites at V1a and V2 receptors ranged from approximately 3-50% and 50-100% that of conivaptan, respectively.
Half Life 5 hours
Dosage Forms Not Available
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions Not Available
Food Interactions Not Available
Pathways Not Available
General References
  1. [PubMed Link Image]
  2. Wikipedia Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 3A4 (CYP3A4)
Targets
  1. Vasopressin V1a receptor
  2. Vasopressin V2 receptor
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 3A4 (CYP3A4)
Enzyme 1 Gene Name CYP3A4
Enzyme 1 SwissProt ID P08684 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P08684|CP3A4_HUMAN Cytochrome P450 3A4 (EC 1.14.13.67) 
ALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMFD
MECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISIA
EDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYSM
DVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICVF
PREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSII
FIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVN
ETLRLFPIAMRLERVCKKDVEINGMFIPKGWVVMIPSYALHRDPKYWTEPEKFLPERFSK
KNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLGG
LLQPEKPVVLKVESRDGTVSGA
Drug Target 1 [top]
Target 1 ID 185
Target 1 Name Vasopressin V1a receptor
Target 1 Synonyms
  1. AVPR V1a
  2. Antidiuretic hormone receptor 1a
  3. V1aR
  4. Vascular/hepatic-type arginine vasopressin receptor
Target 1 Gene Name AVPR1A
Target 1 Protein Sequence >Vasopressin V1a receptor 
MRLSAGPDAGPSGNSSPWWPLATGAGNTSREAEALGEGNGPPRDVRNEELAKLEIAVLAV
TFAVAVLGNSSVLLALHRTPRKTSRMHLFIRHLSLADLAVAFFQVLPQMCWDITYRFRGP
DWLCRVVKHLQVFGMFASAYMLVVMTADRYIAVCHPLKTLQQPARRSRLMIAAAWVLSFV
LSTPQYFVFSMIEVNNVTKARDCWATFIQPWGSRAYVTWMTGGIFVAPVVILGTCYGFIC
YNIWCNVRGKTASRQSKGAEQAGVAFQKGFLLAPCVSSVKSISRAKIRTVKMTFVIVTAY
IVCWAPFFIIQMWSVWDPMSVWTESENPTITITALLGSLNSCCNPWIYMFFSGHLLQDCV
QSFPCCQNMKEKFNKEDTDSMSRRQTFYSNNRSPTNSTGMWKDSPKSSKSIKFIPVST
Target 1 Number of Residues 424
Target 1 Molecular Weight 46800
Target 1 Theoretical pI 9.67
Target 1 GO Classification
Function
peptide receptor activity, G-protein coupled
vasopressin-like receptor activity
vasopressin receptor activity
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 1 General Function Involved in rhodopsin-like receptor activity
Target 1 Specific Function Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate a phosphatidyl- inositol-calcium second messenger system. Has been involved in social behaviors, including affiliation and attachment
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 53-76
  • 89-110
  • 126-147
  • 169-190
  • 219-239
  • 294-313
  • 332-351
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 667068 Link Image
Target 1 UniProtKB/Swiss-Prot ID P37288 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name V1AR_HUMAN Link Image
Target 1 PDB ID 1YTV Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >1257 bp 
ATGCGTCTCTCCGCCGGTCCCGACGCGGGGCCCTCGGGCAACTCCAGCCCATGGTGGCCT
CTGGCCACCGGCGCTGGCAACACAAGCCGGGAGGCCGAAGCCCTCGGGGAGGGCAACGGC
CCACCGAGGGACGTGCGCAACGAGGAGCTGGCCAAACTGGAGATCGCCGTGCTGGCGGTG
ACTTTCGCGGTGGCCGTGCTGGGCAACAGCAGCGTACTGCTGGCTCTGCACCGGACGCCG
CGCAAGACGTCCCGCATGCACCTCTTCATCCGACACCTCAGCCTGGCCGACCTGGCCGTG
GCATTCTTCCAGGTGCTGCCGCAAATGTGCTGGGACATCACCTACCGCTTCCGCGGCCCC
GACTGGCTGTGCCGCGTGGTGAAGCACCTGCAGGTGTTCGGCATGTTTGCGTCGGCCTAC
ATGCTGGTAGTCATGACAGCCGACCGCTACATCGCGGTGTGCCACCCGCTCAAGACTCTG
CAACAGCCCGCGCGCCGCTCGCGCCTCATGATCGCGGCCGCCTGGGTGCTGAGCTTCGTG
CTGAGCACGCCGCAGTACTTCGTCTTCTCCATGATCGAGGTGAACAATGTCACCAAGGCC
CGCGACTGCTGGGCCACCTTCATCCAGCCCTGGGGTTCTCGTGCCTACGTGACCTGGATG
ACGGGCGGCATCTTTGTGGCGCCCGTGGTCATCTTGGGTACCTGCTACGGCTTCATCTGC
TACAACATCTGGTGCAACGTCCGCGGGAAGACGGCGTCGCGCCAGAGCAAGGGTGCAGAG
CAAGCGGGTGTGGCCTTCCAAAAGGGGTTCCTGCTCGCACCCTGTGTCAGCAGCGTGAAG
TCCATTTCCCGGGCCAAGATCCGCACGGTGAAGATGACTTTTGTGATCGTGACGGCTTAC
ATCGTCTGCTGGGCGCCTTTCTTCATCATCCAGATGTGGTCTGTCTGGGATCCCATGTCC
GTCTGGACCGAATCGGAAAACCCTACCATCACCATCACTGCATTACTGGGTTCCTTGAAT
AGCTGCTGTAATCCCTGGATATACATGTTTTTTAGTGGCCATCTCCTTCAAGACTGTGTT
CAAAGCTTCCCATGCTGCCAAAACATGAAGGAAAAATTCAACAAAGAAGATACTGACAGT
ATGAGCAGAAGACAGACTTTTTATTCTAACAATCGAAGCCCAACAAACAGTACGGGTATG
TGGAAGGACTCGCCTAAATCTTCCAAGTCCATCAAATTCATTCCTGTTTCAACTTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID AVPR1A Link Image
Target 1 GenAtlas ID AVPR1A Link Image
Target 1 HGNC ID HGNC:895 Link Image
Target 1 Chromosome Location 12
Target 1 Locus 12q14-q15
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Hirasawa A, Shibata K, Kotosai K, Tsujimoto G: Cloning, functional expression and tissue distribution of human cDNA for the vascular-type vasopressin receptor. Biochem Biophys Res Commun. 1994 Aug 30;203(1):72-9. [PubMed Link Image]
  2. Thibonnier M, Auzan C, Madhun Z, Wilkins P, Berti-Mattera L, Clauser E: Molecular cloning, sequencing, and functional expression of a cDNA encoding the human V1a vasopressin receptor. J Biol Chem. 1994 Feb 4;269(5):3304-10. [PubMed Link Image]
  3. North WG, Fay MJ, Longo K, Du J: Functional vasopressin V1 type receptors are present in variant as well as classical forms of small-cell carcinoma. Peptides. 1997;18(7):985-93. [PubMed Link Image]
  4. North WG, Fay MJ, Longo KA, Du J: Expression of all known vasopressin receptor subtypes by small cell tumors implies a multifaceted role for this neuropeptide. Cancer Res. 1998 May 1;58(9):1866-71. [PubMed Link Image]
Target 1 Drug References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 322
Target 2 Name Vasopressin V2 receptor
Target 2 Synonyms
  1. AVPR V2
  2. Antidiuretic hormone receptor
  3. Renal-type arginine vasopressin receptor
Target 2 Gene Name AVPR2
Target 2 Protein Sequence >Vasopressin V2 receptor 
MLMASTTSAVPGHPSLPSLPSNSSQERPLDTRDPLLARAELALLSIVFVAVALSNGLVLA
ALARRGRRGHWAPIHVFIGHLCLADLAVALFQVLPQLAWKATDRFRGPDALCRAVKYLQM
VGMYASSYMILAMTLDRHRAICRPMLAYRHGSGAHWNRPVLVAWAFSLLLSLPQLFIFAQ
RNVEGGSGVTDCWACFAEPWGRRTYVTWIALMVFVAPTLGIAACQVLIFREIHASLVPGP
SERPGGRRRGRRTGSPGEGAHVSAAVAKTVRMTLVIVVVYVLCWAPFFLVQLWAAWDPEA
PLEGAPFVLLMLLASLNSCTNPWIYASFSSSVSSELRSLLCCARGRTPPSLGPQDESCTT
ASSSLAKDTSS
Target 2 Number of Residues 377
Target 2 Molecular Weight 40279
Target 2 Theoretical pI 9.41
Target 2 GO Classification
Function
peptide receptor activity, G-protein coupled
vasopressin-like receptor activity
vasopressin receptor activity
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 2 General Function Involved in rhodopsin-like receptor activity
Target 2 Specific Function Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate adenylate cyclase
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • 39-63
  • 78-98
  • 114-135
  • 160-180
  • 201-220
  • 272-293
  • 309-328
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 28418 Link Image
Target 2 UniProtKB/Swiss-Prot ID P30518 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name V2R_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 2 Gene Sequence >1116 bp 
ATGCTCATGGCGTCCACCACTTCCGCTGTGCCTGGGCATCCCTCTCTGCCCAGCCTGCCC
AGCAACAGCAGCCAGGAGAGGCCACTGGACACCCGGGACCCGCTGCTAGCCCGGGCGGAG
CTGGCGCTGCTCTCCATAGTCTTTGTGGCTGTGGCCCTGAGCAATGGCCTGGTGCTGGCG
GCCCTAGCTCGGCGGGGCCGGCGGGGCCACTGGGCACCCATACACGTCTTCATTGGCCAC
TTGTGCCTGGCCGACCTGGCCGTGGCTCTGTTCCAAGTGCTGCCCCAGCTGGCCTGGAAG
GCCACCGACCGCTTCCGTGGGCCAGATGCCCTGTGTCGGGCCGTGAAGTATCTGCAGATG
GTGGGCATGTATGCCTCCTCCTACATGATCCTGGCCATGACGCTGGACCGCCACCGTGCC
ATCTGCCGTCCCATGCTGGCGTACCGCCATGGAAGTGGGGCTCACTGGAACCGGCCGGTG
CTAGTGGCTTGGGCCTTCTCGCTCCTTCTCAGCCTGCCCCAGCTCTTCATCTTCGCCCAG
CGCAACGTGGAAGGTGGCAGCGGGGTCACTGACTGCTGGGCCTGCTTTGCGGAGCCCTGG
GGCCGTCGCACCTATGTCACCTGGATTGCCCTGATGGTGTTCGTGGCACCTACCCTGGGT
ATCGCCGCCTGCCAGGTGCTCATCTTCCGGGAGATTCATGCCAGTCTGGTGCCAGGGCCA
TCAGAGAGGCCTGGGGGGCGCCGCAGGGGACGCCGGACAGGCAGCCCCGGTGAGGGAGCC
CACGTGTCAGCAGCTGTGGCCAAGACTGTGAGGATGACGCTAGTGATTGTGGTCGTCTAT
GTGCTGTGCTGGGCACCCTTCTTCCTGGTGCAGCTGTGGGCCGCGTGGGACCCGGAGGCA
CCTCTGGAAGGGGCGCCCTTTGTGCTACTCATGTTGCTGGCCAGCCTCAACAGCTGCACC
AACCCCTGGATCTATGCATCTTTCAGCAGCAGCGTGTCCTCAGAGCTGCGAAGCTTGCTC
TGCTGTGCCCGGGGACGCACCCCACCCAGCCTGGGTCCCCAAGATGAGTCCTGCACCACC
GCCAGCTCCTCCCTGGCCAAGGACACTTCATCGTGA
Target 2 GenBank Gene ID
Target 2 GeneCard ID AVPR2 Link Image
Target 2 GenAtlas ID AVPR2 Link Image
Target 2 HGNC ID HGNC:897 Link Image
Target 2 Chromosome Location X
Target 2 Locus Xq28
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Pasel K, Schulz A, Timmermann K, Linnemann K, Hoeltzenbein M, Jaaskelainen J, Gruters A, Filler G, Schoneberg T: Functional characterization of the molecular defects causing nephrogenic diabetes insipidus in eight families. J Clin Endocrinol Metab. 2000 Apr;85(4):1703-10. [PubMed Link Image]
  2. Postina R, Ufer E, Pfeiffer R, Knoers NV, Fahrenholz F: Misfolded vasopressin V2 receptors caused by extracellular point mutations entail congential nephrogenic diabetes insipidus. Mol Cell Endocrinol. 2000 Jun;164(1-2):31-9. [PubMed Link Image]
  3. Inaba S, Hatakeyama H, Taniguchi N, Miyamori I: The property of a novel v2 receptor mutant in a patient with nephrogenic diabetes insipidus. J Clin Endocrinol Metab. 2001 Jan;86(1):381-5. [PubMed Link Image]
  4. Chen CH, Chen WY, Liu HL, Liu TT, Tsou AP, Lin CY, Chao T, Qi Y, Hsiao KJ: Identification of mutations in the arginine vasopressin receptor 2 gene causing nephrogenic diabetes insipidus in Chinese patients. J Hum Genet. 2002;47(2):66-73. [PubMed Link Image]
  5. Pan Y, Metzenberg A, Das S, Jing B, Gitschier J: Mutations in the V2 vasopressin receptor gene are associated with X-linked nephrogenic diabetes insipidus. Nat Genet. 1992 Oct;2(2):103-6. [PubMed Link Image]
  6. van den Ouweland AM, Dreesen JC, Verdijk M, Knoers NV, Monnens LA, Rocchi M, van Oost BA: Mutations in the vasopressin type 2 receptor gene (AVPR2) associated with nephrogenic diabetes insipidus. Nat Genet. 1992 Oct;2(2):99-102. [PubMed Link Image]
  7. Rosenthal W, Seibold A, Antaramian A, Lonergan M, Arthus MF, Hendy GN, Birnbaumer M, Bichet DG: Molecular identification of the gene responsible for congenital nephrogenic diabetes insipidus. Nature. 1992 Sep 17;359(6392):233-5. [PubMed Link Image]
  8. Birnbaumer M, Seibold A, Gilbert S, Ishido M, Barberis C, Antaramian A, Brabet P, Rosenthal W: Molecular cloning of the receptor for human antidiuretic hormone. Nature. 1992 May 28;357(6376):333-5. [PubMed Link Image]
  9. Tsukaguchi H, Matsubara H, Taketani S, Mori Y, Seido T, Inada M: Binding-, intracellular transport-, and biosynthesis-defective mutants of vasopressin type 2 receptor in patients with X-linked nephrogenic diabetes insipidus. J Clin Invest. 1995 Oct;96(4):2043-50. [PubMed Link Image]
  10. Faa V, Ventruto ML, Loche S, Bozzola M, Podda R, Cao A, Rosatelli MC: Mutations in the vasopressin V2-receptor gene in three families of Italian descent with nephrogenic diabetes insipidus. Hum Mol Genet. 1994 Sep;3(9):1685-6. [PubMed Link Image]
  11. 7984150 Birnbaumer M, Gilbert S, Rosenthal W: An extracellular congenital nephrogenic diabetes insipidus mutation of the vasopressin receptor reduces cell surface expression, affinity for ligand, and coupling to the Gs/adenylyl cyclase system. Mol Endocrinol. 1994 Jul;8(7):886-94.
  12. 7987330 Wenkert D, Merendino JJ Jr, Shenker A, Thambi N, Robertson GL, Moses AM, Spiegel AM: Novel mutations in the V2 vasopressin receptor gene of patients with X-linked nephrogenic diabetes insipidus. Hum Mol Genet. 1994 Aug;3(8):1429-30.
  13. 7999078 Oksche A, Dickson J, Schulein R, Seyberth HW, Muller M, Rascher W, Birnbaumer M, Rosenthal W: Two novel mutations in the vasopressin V2 receptor gene in patients with congenital nephrogenic diabetes insipidus. Biochem Biophys Res Commun. 1994 Nov 30;205(1):552-7.
  14. 8037205 Bichet DG, Birnbaumer M, Lonergan M, Arthus MF, Rosenthal W, Goodyer P, Nivet H, Benoit S, Giampietro P, Simonetti S, et al.: Nature and recurrence of AVPR2 mutations in X-linked nephrogenic diabetes insipidus. Am J Hum Genet. 1994 Aug;55(2):278-86.
  15. 8045948 Yuasa H, Ito M, Oiso Y, Kurokawa M, Watanabe T, Oda Y, Ishizuka T, Tani N, Ito S, Shibata A, et al.: Novel mutations in the V2 vasopressin receptor gene in two pedigrees with congenital nephrogenic diabetes insipidus. J Clin Endocrinol Metab. 1994 Aug;79(2):361-5.
  16. 8078903 Friedman E, Bale AE, Carson E, Boson WL, Nordenskjold M, Ritzen M, Ferreira PC, Jammal A, De Marco L: Nephrogenic diabetes insipidus: an X chromosome-linked dominant inheritance pattern with a vasopressin type 2 receptor gene that is structurally normal. Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8457-61.
  17. 8267567 Tsukaguchi H, Matsubara H, Aritaki S, Kimura T, Abe S, Inada M: Two novel mutations in the vasopressin V2 receptor gene in unrelated Japanese kindreds with nephrogenic diabetes insipidus. Biochem Biophys Res Commun. 1993 Dec 15;197(2):1000-10.
  18. 8479490 Holtzman EJ, Harris HW Jr, Kolakowski LF Jr, Guay-Woodford LM, Botelho B, Ausiello DA: Brief report: a molecular defect in the vasopressin V2-receptor gene causing nephrogenic diabetes insipidus. N Engl J Med. 1993 May 27;328(21):1534-7.
  19. 8514744 Rosenthal W, Antaramian A, Gilbert S, Birnbaumer M: Nephrogenic diabetes insipidus. A V2 vasopressin receptor unable to stimulate adenylyl cyclase. J Biol Chem. 1993 Jun 25;268(18):13030-3.
  20. 8735975 Fay MJ, Du J, Yu X, North WG: Evidence for expression of vasopressin V2 receptor mRNA in human lung. Peptides. 1996;17(3):477-81.
  21. 9224808 Sadeghi HM, Innamorati G, Dagarag M, Birnbaumer M: Palmitoylation of the V2 vasopressin receptor. Mol Pharmacol. 1997 Jul;52(1):21-9.
  22. 9402087 Vargas-Poussou R, Forestier L, Dautzenberg MD, Niaudet P, Dechaux M, Antignac C: Mutations in the vasopressin V2 receptor and aquaporin-2 genes in 12 families with congenital nephrogenic diabetes insipidus. J Am Soc Nephrol. 1997 Dec;8(12):1855-62.
  23. 9452109 Shoji Y, Takahashi T, Suzuki Y, Suzuki T, Komatsu K, Hirono H, Shoji Y, Yokoyama T, Kito H, Takada G: Mutational analyses of AVPR2 gene in three Japanese families with X-linked nephrogenic diabetes insipidus: two recurrent mutations, R137H and deltaV278, caused by the hypermutability at CpG dinucleotides. Hum Mutat. 1998;Suppl 1:S278-83.
  24. 9581826 North WG, Fay MJ, Longo KA, Du J: Expression of all known vasopressin receptor subtypes by small cell tumors implies a multifaceted role for this neuropeptide. Cancer Res. 1998 May 1;58(9):1866-71.
  25. 9711877 Schoneberg T, Schulz A, Biebermann H, Gruters A, Grimm T, Hubschmann K, Filler G, Gudermann T, Schultz G: V2 vasopressin receptor dysfunction in nephrogenic diabetes insipidus caused by different molecular mechanisms. Hum Mutat. 1998;12(3):196-205.
Target 2 Drug References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
  2. Wada K, Fujimori A, Matsukawa U, Arai Y, Sudoh K, Yatsu T, Sasamata M, Miyata K: Intravenous administration of conivaptan hydrochloride improves cardiac hemodynamics in rats with myocardial infarction-induced congestive heart failure. Eur J Pharmacol. 2005 Jan 10;507(1-3):145-51. Epub 2005 Jan 1. [PubMed Link Image]
  3. Palm C, Pistrosch F, Herbrig K, Gross P: Vasopressin antagonists as aquaretic agents for the treatment of hyponatremia. Am J Med. 2006 Jul;119(7 Suppl 1):S87-92. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.