Page last updated: 2024-11-07

conivaptan

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Description

conivaptan : The amide resulting from the formal condensation of 4-[(biphenyl-2-ylcarbonyl)amino]benzoic acid with the benzazepine nitrogen of 2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepine. It is an antagonist for two of the three types of arginine vasopressin (AVP) receptors, V1a and V2. It is used as its hydrochloride salt for the treatment of hyponatraemia (low blood sodium levels) caused by syndrome of inappropriate antidiuretic hormone (SIADH). [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID151171
CHEMBL ID1755
CHEBI ID681850
SCHEMBL ID49815
MeSH IDM0387075

Synonyms (56)

Synonym
gtpl2203
n-[4-(2-methyl4,5-dihydro-3h-imidazo[5,4-d][1]benzazepine-6-carbonyl)phenyl]-2-phenylbenzamide
PDSP1_001735
PDSP2_001718
4'-((4,5-dihydro-2-methylimidazo(4,5-d)(1)benzazepin-6(1h)-yl)carbonyl)-2-biphenylcarboxanilide
DB00872
conivaptan
ym087
L001531
L001073
n-[4-(2-methyl-4,5-dihydro-3h-imidazo[4,5-d][1]benzazepine-6-carbonyl)phenyl]-2-phenylbenzamide
CHEBI:681850 ,
D07748
n-{4-[(2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1h)-yl)carbonyl]phenyl}biphenyl-2-carboxamide
conivaptan (inn)
210101-16-9
CHEMBL1755
4''-((4,5-dihydro-2-methylimidazo(4,5-d)(1)benzazepin-6(1h)-yl)carbonyl)-2-biphenylcarboxanilide
(1,1'-biphenyl)-2-carboxamide, n-(4-((4,5-dihydro-2-methylimidazo(4,5-d)(1)benzazepin-6(1h)-yl)carbonyl)phenyl)-
unii-0nj98y462x
conivaptan [inn]
(1,1'-biphenyl)-2-carboxamide, n-(4-(4,5-dihydro-2-methylimidazo(4,5-d)(1)benzazepin-6(1h)-yl)carbonyl)phenyl)-
0nj98y462x ,
bdbm85095
cas_151171
nsc_151171
AKOS015917893
NCGC00345881-02
conivaptan [mi]
conivaptan [vandf]
conivaptan [who-dd]
SCHEMBL49815
[1,1'-biphenyl]-2-carboxamide, n-[4-[(4,5-dihydro-2-methylimidazo[4,5-d][1]benzazepin-6(1h)-yl)carbonyl]phenyl]-
AM20090722
IKENVDNFQMCRTR-UHFFFAOYSA-N
4'-[(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepin-6-yl)carbonyl]-2-phenylbenzanilide
AC-30626
AB01565868_02
DTXSID80175220 ,
n-[4-({4-methyl-3,5,9-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),2(6),3,11,13-pentaen-9-yl}carbonyl)phenyl]-2-phenylbenzamide
AKOS027326517
NCGC00345881-05
BCP07817
Q5161126
FT-0724257
n-[4-[(4,5-dihydro-2-methylimidazo[4,5-d][benzazepin-6(1h)-yl)carbonyl]phenyl-[1,1'-biphenyl]-2-carboxamide hydrochloride
HMS3745C21
NCGC00345881-04
NCGC00345881-03
EN300-6481317
n-(4-{4-methyl-3,5,9-triazatricyclo[8.4.0.0,2,6]tetradeca-1(10),2(6),3,11,13-pentaene-9-carbonyl}phenyl)-[1,1'-biphenyl]-2-carboxamide
Z2588038959
n-(4-((2-methyl-4,5-dihydroimidazo(4,5-d)(1)benzazepin-6(1h)-yl)carbonyl)phenyl)biphenyl-2-carboxamide
dtxcid3097711
c03xa02
conivaptanum

Research Excerpts

Overview

Conivaptan is a non-peptide dual antagonist of vasopressin V1A and V2 receptors. It is approved in the United States as an intravenous formulation for the treatment of euvolemic and hypervolemic hyponatremia in hospitalized patients.

ExcerptReferenceRelevance
"Conivaptan is a non-peptide dual antagonist of vasopressin V1A and V2 receptors that is approved in the United States as an intravenous formulation for the treatment of euvolemic and hypervolemic hyponatremia in hospitalized patients. "( Pharmacokinetics of intravenous conivaptan in subjects with hepatic or renal impairment.
Abeyratne, AT; Erdman, KA; Keirns, JJ; Lasseter, K; Plumb, LC; Riff, DS; Roy, MJ, 2013
)
2.12
"Conivaptan is a potentially useful treatment option for hyponatremia in the setting of Cushing's disease patients after pituitary surgery."( Use of conivaptan for management of hyponatremia following surgery for Cushing's disease.
Blevins, LS; Breshears, JD; Jiang, B; Kunwar, S; Rowland, NC, 2013
)
2.29
"Conivaptan is an FDA-approved vasopressin receptor antagonist that may exert both osmotic and anti-inflammatory effects."( The Effects of Clinically Relevant Hypertonic Saline and Conivaptan Administration on Ischemic Stroke.
Collier, L; Decker, D; Lau, T; Leonardo, C; Olivera, R; Pennypacker, KR; Roma, G; Rowe, D; Seifert, H, 2016
)
1.4
"*Conivaptan is an arginine vasopressin V1A and V2 receptor antagonist. "( Intravenous conivaptan.
Keating, GM; Moen, MD, 2008
)
1.64
"Conivaptan is an effective and FDA approved for the treatment of euvolemic and hypervolemic hyponatremia and may offer an extra treatment option in HF by targeting V(1a) and V(2) receptors."( Conivaptan: promise of treatment in heart failure.
Afiniwala, M; Arumugham, P; Hoque, MZ; Huda, N; Karia, DH; Verma, N, 2009
)
2.52
"Conivaptan is a nonpeptide vasopressin V(1A)/V(2)-receptor antagonist that produces a controlled increase in serum sodium concentration in hospitalized patients with euvolemic or hyper-volemic hyponatremia."( Pharmacokinetics of conivaptan hydrochloride, a vasopressin V(1A)/V(2)-receptor antagonist, in patients with euvolemic or hypervolemic hyponatremia and with or without congestive heart failure from a prospective, 4-day open-label study.
Keirns, J; Mao, ZL; Stalker, D, 2009
)
2.12
"Conivaptan is a nonselective AVP antagonist that is available intravenously, and tolvaptan is a V2 selective AVP antagonist that is available as an oral tablet."( Novel agents for the treatment of hyponatremia: a review of conivaptan and tolvaptan.
Ferguson-Myrthil, N,
)
1.09
"Conivaptan is an arginine-vasopressin-receptor antagonist approved for the treatment of hyponatremia. "( Open-label randomized trial of the safety and efficacy of a single dose conivaptan to raise serum sodium in patients with traumatic brain injury.
Chesnut, R; Dagal, A; Deem, S; Galton, C; Souter, M; Treggiari, M; Yanez, ND, 2011
)
2.04
"Conivaptan is an arginine vasopressin receptor antagonist that has been shown to be both safe and effective in the treatment of euvolemic and hypervolemic hyponatremia."( Use of intravenous conivaptan in neurosurgical patients with hyponatremia from syndrome of inappropriate antidiuretic hormone secretion.
Blevins, LS; DeGiacomo, AF; Deragopian, L; Potts, MB, 2011
)
1.42
"Conivaptan is a nonspecific arginine vasopressin receptor antagonist that has been used as therapy in adults who have hypervolemic hyponatremia due to congestive heart failure. "( Conivaptan therapy in an infant with severe hyponatremia and congestive heart failure.
Balaguru, D; Bricker, JT; Haque, I; Pham-Peyton, C; Sahu, R; Thapar, V, 2012
)
3.26
"Conivaptan, which is a dual antagonist of the V1a and V2 receptor, has shown promise in animal studies and in small scale human trials as a potential therapeutic option for the treatment of acute and chronic heart failure."( Conivaptan: a selective vasopressin antagonist for the treatment of heart failure.
Sanghi, P; Schwarz, ER, 2006
)
2.5
"Conivaptan is a combined V(1A)/V(2)-receptor antagonist that induces diuresis as well as haemodynamic improvement."( Therapeutic potential of vasopressin receptor antagonists.
Ali, F; Ghali, JK; Guglin, M; Vaitkevicius, P, 2007
)
1.06
"Conivaptan hydrochloride is a nonpeptide, V1A and V2 vasopressin-receptor antagonist. "( Conivaptan: new treatment for hyponatremia.
Walter, KA, 2007
)
3.23
"Conivaptan is a nonpeptide dual V1a/V2 AVP receptor antagonist."( Conivaptan: a dual vasopressin receptor v1a/v2 antagonist [corrected].
Ali, F; Ghali, JK; Raufi, MA; Washington, B, 2007
)
2.5
"Conivaptan is a high-affinity, nonpeptide vasopressin V(1A)/V(2)-receptor antagonist."( Assessment of the efficacy and safety of intravenous conivaptan in patients with euvolaemic hyponatraemia: subgroup analysis of a randomized, controlled study.
Andoh, M; Barve, A; Smith, N; Verbalis, JG; Zeltser, D, 2008
)
1.32
"Conivaptan is a vasopressin 1a and 2 receptor antagonist recently approved by the US Food and Drug Administration (FDA) for treating euvolemic and hypervolemic hyponatremia in adult patients."( Use of conivaptan to allow aggressive hydration to prevent tumor lysis syndrome in a pediatric patient with large-cell lymphoma and SIADH.
Cain, JP; Rianthavorn, P; Turman, MA, 2008
)
1.52
"Conivaptan is a V1a/V2 non-selective vasopressin-receptor antagonist that has been approved by the US Food and Drug Administration as an intravenous infusion for the inhospital treatment of euvolaemic or hypervolaemic hyponatraemia."( Non-peptide arginine-vasopressin antagonists: the vaptans.
Decaux, G; Soupart, A; Vassart, G, 2008
)
1.07

Effects

Conivaptan has been approved by the US Food and Drug Administration for short-term intravenous treatment of euvolemic hyponatremia of variable etiology. It has not been adequately studied in heart failure.

ExcerptReferenceRelevance
"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."( Vasopressin and vasopressin antagonists in heart failure and hyponatremia.
Farmakis, D; Filippatos, G; Gheorghiade, M; Kremastinos, DT, 2008
)
1.07
"Conivaptan has been shown to correct hyponatremia in euvolemic or hypervolemic patients."( Conivaptan: a dual vasopressin receptor v1a/v2 antagonist [corrected].
Ali, F; Ghali, JK; Raufi, MA; Washington, B, 2007
)
2.5

Treatment

ExcerptReferenceRelevance
"Treatment with conivaptan elevated serum osmolality in a dose-dependent manner. "( Conivaptan, a Selective Arginine Vasopressin V1a and V2 Receptor Antagonist Attenuates Global Cerebral Edema Following Experimental Cardiac Arrest via Perivascular Pool of Aquaporin-4.
Amiry-Moghaddam, M; Bhardwaj, A; Nakayama, S; Ottersen, OP, 2016
)
2.23

Toxicity

Conivaptan was well tolerated; the most frequent adverse events were urinary tract infection, anemia, pyrexia, cardiac failure, hypotension, and hypokalemia. These data suggest that a single dose conivptan is safe in non-hyponatremic patients with severe TBI and may reduce ICP.

ExcerptReferenceRelevance
" Headache, hypotension, nausea, constipation, and postural hypotension were the most common adverse events."( Efficacy and safety of oral conivaptan: a V1A/V2 vasopressin receptor antagonist, assessed in a randomized, placebo-controlled trial in patients with euvolemic or hypervolemic hyponatremia.
Brooks-Asplund, E; Fan, K; Ghali, JK; Koren, MJ; Long, WA; Smith, N; Taylor, JR, 2006
)
0.63
" Safety assessments included adverse events (AE), incidence of overly rapid correction of serum [Na(+)], and changes in vital signs and electrocardiographic and clinical laboratory parameters."( Assessment of the efficacy and safety of intravenous conivaptan in patients with euvolaemic hyponatraemia: subgroup analysis of a randomized, controlled study.
Andoh, M; Barve, A; Smith, N; Verbalis, JG; Zeltser, D, 2008
)
0.6
" The most common adverse events were infusion-site reactions."( Efficacy and safety of the vasopressin V1A/V2-receptor antagonist conivaptan in acute decompensated heart failure: a dose-ranging pilot study.
Barve, A; Elkayam, U; Goldsmith, SR; Haught, WH; He, W, 2008
)
0.58
" Conivaptan was well tolerated; the most frequent adverse events were urinary tract infection, anemia, pyrexia, cardiac failure, hypotension, and hypokalemia."( Efficacy and safety of oral conivaptan, a vasopressin-receptor antagonist, evaluated in a randomized, controlled trial in patients with euvolemic or hypervolemic hyponatremia.
Annane, D; Decaux, G; Smith, N, 2009
)
1.56
" We hypothesized that administration of conivaptan to normonatremic patients with traumatic brain injury (TBI) is safe and could reduce intracranial pressure (ICP)."( Open-label randomized trial of the safety and efficacy of a single dose conivaptan to raise serum sodium in patients with traumatic brain injury.
Chesnut, R; Dagal, A; Deem, S; Galton, C; Souter, M; Treggiari, M; Yanez, ND, 2011
)
0.87
" The primary endpoint was the evaluation of the safety profile defined by serum sodium increases averaging >1 mEq/h when measured every 4 h and any adverse events."( Open-label randomized trial of the safety and efficacy of a single dose conivaptan to raise serum sodium in patients with traumatic brain injury.
Chesnut, R; Dagal, A; Deem, S; Galton, C; Souter, M; Treggiari, M; Yanez, ND, 2011
)
0.6
" There were no drug-related serious adverse events."( Open-label randomized trial of the safety and efficacy of a single dose conivaptan to raise serum sodium in patients with traumatic brain injury.
Chesnut, R; Dagal, A; Deem, S; Galton, C; Souter, M; Treggiari, M; Yanez, ND, 2011
)
0.6
"These data suggest that a single dose conivaptan is safe in non-hyponatremic patients with severe TBI and may reduce ICP."( Open-label randomized trial of the safety and efficacy of a single dose conivaptan to raise serum sodium in patients with traumatic brain injury.
Chesnut, R; Dagal, A; Deem, S; Galton, C; Souter, M; Treggiari, M; Yanez, ND, 2011
)
0.87
" Overall, adverse events related to general disorders and ISRs occurred in 39%, 43%, 53%, and 55% of patients receiving regimens 1, 2, 3, and 4, respectively."( Effect of loading dose and formulation on safety and efficacy of conivaptan in treatment of euvolemic and hypervolemic hyponatremia.
Abeyratne, A; Arthur, JM; Efrati, S; Kalra, S; Klasen, S; McNutt, BE; Oliven, A; Velez, JC, 2011
)
0.61
" Conivaptan was generally well tolerated, with infusion-site reactions being the most common adverse effects (AEs)."( Efficacy and safety of 30-minute infusions of conivaptan in euvolemic and hypervolemic hyponatremia.
Abeyratne, A; Hamad, A; Kalra, S; Klasen, S; Koren, MJ; McNutt, BE, 2011
)
1.54
" Safety was evaluated by the incidence of adverse events, changes in vital signs and laboratory parameters, rate of sNa correction, and frequency of infusion-site reactions."( Dose comparison of conivaptan (Vaprisol®) in patients with euvolemic or hypervolemic hyponatremia--efficacy, safety, and pharmacokinetics.
Palmer, BF; Rock, AD; Woodward, EJ, 2016
)
0.76
"Both 20 and 40 mg/day doses of conivaptan are efficacious in increasing sNa over 4 days of treatment with no observed increase in the frequency of adverse events or specific infusion-site reactions using the higher dose."( Dose comparison of conivaptan (Vaprisol®) in patients with euvolemic or hypervolemic hyponatremia--efficacy, safety, and pharmacokinetics.
Palmer, BF; Rock, AD; Woodward, EJ, 2016
)
1.05
" All patients survived to follow-up, and adverse event rates were comparable with those of the neurocritical care unit overall."( Conivaptan for the Reduction of Cerebral Edema in Intracerebral Hemorrhage: A Safety and Tolerability Study.
Asaithambi, G; Banerji, N; Castle, AL; Corry, JJ; Ho, BM; Lassig, JP; Marino, EH; Shaik, AM; Tipps, ME, 2020
)
2

Pharmacokinetics

ExcerptReferenceRelevance
"The pharmacokinetic and pharmacodynamic properties of YM087, (4'-[(2-methyl-1,4,5,6- tetrahydroimidazo[4,5-d][1]benzazepin-6-yl)-carbonyl]-2-p henylbenzanilide monohydrochloride), a new orally active, dual V1/V2 receptor antagonist were characterised in healthy normotensive subjects."( Pharmacokinetic and pharmacodynamic effects of YM087, a combined V1/V2 vasopressin receptor antagonist in normal subjects.
Brunner, HR; Burnier, M; Fricker, AF; Hayoz, D; Nussberger, J, 1999
)
0.3
" pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data."( Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
Lombardo, F; Obach, RS; Waters, NJ, 2008
)
0.35
" A subset of patients at 2 study sites (the "pharmacokineticrich" subset) provided additional samples for pharmacokinetic analysis on day 1 at 1, 4, and 24 hours; on day 2 at 24 hours; and on day 5 at 1, 2, 7, 12, and 24 hours."( Pharmacokinetics of conivaptan hydrochloride, a vasopressin V(1A)/V(2)-receptor antagonist, in patients with euvolemic or hypervolemic hyponatremia and with or without congestive heart failure from a prospective, 4-day open-label study.
Keirns, J; Mao, ZL; Stalker, D, 2009
)
0.68
"These studies were phase I, open-label pharmacokinetic studies conducted at two sites in the US."( Pharmacokinetics of intravenous conivaptan in subjects with hepatic or renal impairment.
Abeyratne, AT; Erdman, KA; Keirns, JJ; Lasseter, K; Plumb, LC; Riff, DS; Roy, MJ, 2013
)
0.67
"Primary pharmacokinetic parameters estimated were the area under the plasma conivaptan concentration-time curve from time 0 to infinity (AUC∞), plasma conivaptan concentrations at the end of the 20-mg loading dose (C LD), and plasma conivaptan concentrations at the end of the second day 20-mg/24-h continuous infusion (C 48)."( Pharmacokinetics of intravenous conivaptan in subjects with hepatic or renal impairment.
Abeyratne, AT; Erdman, KA; Keirns, JJ; Lasseter, K; Plumb, LC; Riff, DS; Roy, MJ, 2013
)
0.9
" Pharmacokinetic parameters were also measured."( Dose comparison of conivaptan (Vaprisol®) in patients with euvolemic or hypervolemic hyponatremia--efficacy, safety, and pharmacokinetics.
Palmer, BF; Rock, AD; Woodward, EJ, 2016
)
0.76
" The pharmacokinetic parameters of both doses were similar to what has been reported previously, exhibiting greater-than-dose-proportional plasma concentrations."( Dose comparison of conivaptan (Vaprisol®) in patients with euvolemic or hypervolemic hyponatremia--efficacy, safety, and pharmacokinetics.
Palmer, BF; Rock, AD; Woodward, EJ, 2016
)
0.76

Bioavailability

ExcerptReferenceRelevance
"YM087 had an oral bioavailability of 44% and a short half-life."( Pharmacokinetic and pharmacodynamic effects of YM087, a combined V1/V2 vasopressin receptor antagonist in normal subjects.
Brunner, HR; Burnier, M; Fricker, AF; Hayoz, D; Nussberger, J, 1999
)
0.3
"The pharmacology, bioavailability and pharmacokinetics, clinical efficacy, adverse effects and toxicities, drug interactions, dosage and administration, and safety issues related to the use of conivaptan are discussed."( Conivaptan: new treatment for hyponatremia.
Walter, KA, 2007
)
1.97
"Oral bioavailability (F) is a product of fraction absorbed (Fa), fraction escaping gut-wall elimination (Fg), and fraction escaping hepatic elimination (Fh)."( Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
Chang, G; El-Kattan, A; Miller, HR; Obach, RS; Rotter, C; Steyn, SJ; Troutman, MD; Varma, MV, 2010
)
0.36
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019
)
0.51

Dosage Studied

Intermittent dosing of conivaptan was effective in increasing free water excretion and correcting hyponatremia in neurologically ill patients. Conivptan at each dosage increased urine output significantly more than placebo at 24 hours.

ExcerptRelevanceReference
"The pharmacology, bioavailability and pharmacokinetics, clinical efficacy, adverse effects and toxicities, drug interactions, dosage and administration, and safety issues related to the use of conivaptan are discussed."( Conivaptan: new treatment for hyponatremia.
Walter, KA, 2007
)
1.97
" The studies used various dosing regimens for conivaptan but maintained the same efficacy endpoints."( Conivaptan: new treatment for hyponatremia.
Walter, KA, 2007
)
2.04
" Conivaptan at each dosage increased urine output significantly more than placebo at 24 hours (P ( Efficacy and safety of the vasopressin V1A/V2-receptor antagonist conivaptan in acute decompensated heart failure: a dose-ranging pilot study.
Barve, A; Elkayam, U; Goldsmith, SR; Haught, WH; He, W, 2008
)
1.49
"Intermittent dosing of conivaptan was effective in increasing free water excretion and correcting hyponatremia in neurologically ill patients."( Conivaptan bolus dosing for the correction of hyponatremia in the neurointensive care unit.
Dhar, R; Diringer, M; Murphy, T, 2009
)
2.11
"Intravenous vasopressin receptor antagonist is an effective and safe treatment for hyponatremia in the rehabilitation setting if the dosage and monitoring protocols are modified in accordance with the physiology of the patient with spinal cord injury."( Vasopressin receptor antagonist use in a neurologic rehabilitation center.
Bar-Or, D; Garrett, RE; Maerz, G; Wilhelm, S, 2010
)
0.36
" In this case report, we report an extremely rapid correction of serum sodium with a typical dosing regimen of conivaptan."( Extreme correction of hyponatremia in a patient treated with intravenous conivaptan.
Blevins, LS; McDermott, M; Sughrue, ME, 2010
)
0.8
"All four dosing regimens were efficacious, safe, and well tolerated."( Effect of loading dose and formulation on safety and efficacy of conivaptan in treatment of euvolemic and hypervolemic hyponatremia.
Abeyratne, A; Arthur, JM; Efrati, S; Kalra, S; Klasen, S; McNutt, BE; Oliven, A; Velez, JC, 2011
)
0.61
" Average increase in sNa after 4 days was ~10 mEq/L, varying with dosage level and baseline volume status."( Dose comparison of conivaptan (Vaprisol®) in patients with euvolemic or hypervolemic hyponatremia--efficacy, safety, and pharmacokinetics.
Palmer, BF; Rock, AD; Woodward, EJ, 2016
)
0.76
"Vaptans were associated with a significant increase in urine output and serum sodium with an apparent reduction or stabilization of furosemide equivalent dosing in the early treatment period in patients with decompensated RHF."( Vasopressin antagonism for decompensated right-sided heart failure.
Chibnall, JT; Godishala, A; Goff, ZD; Hauptman, PJ; Joseph, SM; Shuster, JE; Vidic, A, 2019
)
0.51
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (2)

RoleDescription
vasopressin receptor antagonistAny drug which blocks vasopressin receptors.
aquareticA class of diuretics which promote aquaresis (the excretion of water without electrolyte loss).
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (1)

ClassDescription
benzazepineA group of two-ring heterocyclic compounds consisting of a benzene ring fused to an azepine ring.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (8)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
cytochrome P450 family 3 subfamily A polypeptide 4Homo sapiens (human)Potency0.30110.01237.983543.2770AID1645841
EWS/FLI fusion proteinHomo sapiens (human)Potency24.81610.001310.157742.8575AID1259253; AID1259255; AID1259256
cytochrome P450 2D6Homo sapiens (human)Potency4.77240.00108.379861.1304AID1645840
Spike glycoproteinSevere acute respiratory syndrome-related coronavirusPotency39.81070.009610.525035.4813AID1479145
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Vasopressin V2 receptorHomo sapiens (human)IC50 (µMol)0.01100.00001.12137.0000AID483985
Vasopressin V2 receptorHomo sapiens (human)Ki0.00040.00040.43453.9811AID483982
Vasopressin V1a receptorHomo sapiens (human)IC50 (µMol)0.00300.00060.38352.0000AID483984
Vasopressin V1a receptorHomo sapiens (human)Ki0.00040.00020.62357.0300AID483981
Vasopressin V1b receptorRattus norvegicus (Norway rat)Ki10.00000.00030.01580.0610AID1386887
Oxytocin receptorRattus norvegicus (Norway rat)Ki10.00000.00090.04890.2300AID1386887
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (36)

Processvia Protein(s)Taxonomy
positive regulation of systemic arterial blood pressureVasopressin V2 receptorHomo sapiens (human)
renal water retentionVasopressin V2 receptorHomo sapiens (human)
adenylate cyclase-modulating G protein-coupled receptor signaling pathwayVasopressin V2 receptorHomo sapiens (human)
activation of adenylate cyclase activityVasopressin V2 receptorHomo sapiens (human)
hemostasisVasopressin V2 receptorHomo sapiens (human)
positive regulation of cell population proliferationVasopressin V2 receptorHomo sapiens (human)
negative regulation of cell population proliferationVasopressin V2 receptorHomo sapiens (human)
positive regulation of gene expressionVasopressin V2 receptorHomo sapiens (human)
telencephalon developmentVasopressin V2 receptorHomo sapiens (human)
response to cytokineVasopressin V2 receptorHomo sapiens (human)
positive regulation of intracellular signal transductionVasopressin V2 receptorHomo sapiens (human)
cellular response to hormone stimulusVasopressin V2 receptorHomo sapiens (human)
positive regulation of vasoconstrictionVasopressin V2 receptorHomo sapiens (human)
G protein-coupled receptor signaling pathwayVasopressin V2 receptorHomo sapiens (human)
regulation of systemic arterial blood pressure by vasopressinVasopressin V2 receptorHomo sapiens (human)
maternal aggressive behaviorVasopressin V1a receptorHomo sapiens (human)
positive regulation of systemic arterial blood pressureVasopressin V1a receptorHomo sapiens (human)
generation of precursor metabolites and energyVasopressin V1a receptorHomo sapiens (human)
activation of phospholipase C activityVasopressin V1a receptorHomo sapiens (human)
positive regulation of cytosolic calcium ion concentrationVasopressin V1a receptorHomo sapiens (human)
negative regulation of female receptivityVasopressin V1a receptorHomo sapiens (human)
grooming behaviorVasopressin V1a receptorHomo sapiens (human)
blood circulationVasopressin V1a receptorHomo sapiens (human)
positive regulation of cell population proliferationVasopressin V1a receptorHomo sapiens (human)
positive regulation of heart rateVasopressin V1a receptorHomo sapiens (human)
positive regulation of glutamate secretionVasopressin V1a receptorHomo sapiens (human)
myotube differentiationVasopressin V1a receptorHomo sapiens (human)
calcium-mediated signalingVasopressin V1a receptorHomo sapiens (human)
telencephalon developmentVasopressin V1a receptorHomo sapiens (human)
positive regulation of cell growthVasopressin V1a receptorHomo sapiens (human)
positive regulation of prostaglandin biosynthetic processVasopressin V1a receptorHomo sapiens (human)
positive regulation of cellular pH reductionVasopressin V1a receptorHomo sapiens (human)
social behaviorVasopressin V1a receptorHomo sapiens (human)
cellular response to water deprivationVasopressin V1a receptorHomo sapiens (human)
maternal behaviorVasopressin V1a receptorHomo sapiens (human)
sperm ejaculationVasopressin V1a receptorHomo sapiens (human)
response to corticosteroneVasopressin V1a receptorHomo sapiens (human)
negative regulation of transmission of nerve impulseVasopressin V1a receptorHomo sapiens (human)
transport across blood-brain barrierVasopressin V1a receptorHomo sapiens (human)
G protein-coupled receptor signaling pathwayVasopressin V1a receptorHomo sapiens (human)
positive regulation of vasoconstrictionVasopressin V1a receptorHomo sapiens (human)
cellular response to hormone stimulusVasopressin V1a receptorHomo sapiens (human)
regulation of systemic arterial blood pressure by vasopressinVasopressin V1a receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (6)

Processvia Protein(s)Taxonomy
vasopressin receptor activityVasopressin V2 receptorHomo sapiens (human)
protein bindingVasopressin V2 receptorHomo sapiens (human)
peptide bindingVasopressin V2 receptorHomo sapiens (human)
vasopressin receptor activityVasopressin V1a receptorHomo sapiens (human)
protein kinase C bindingVasopressin V1a receptorHomo sapiens (human)
protein bindingVasopressin V1a receptorHomo sapiens (human)
peptide hormone bindingVasopressin V1a receptorHomo sapiens (human)
V1A vasopressin receptor bindingVasopressin V1a receptorHomo sapiens (human)
peptide bindingVasopressin V1a receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (9)

Processvia Protein(s)Taxonomy
endosomeVasopressin V2 receptorHomo sapiens (human)
endoplasmic reticulumVasopressin V2 receptorHomo sapiens (human)
Golgi apparatusVasopressin V2 receptorHomo sapiens (human)
plasma membraneVasopressin V2 receptorHomo sapiens (human)
membraneVasopressin V2 receptorHomo sapiens (human)
endocytic vesicleVasopressin V2 receptorHomo sapiens (human)
clathrin-coated endocytic vesicle membraneVasopressin V2 receptorHomo sapiens (human)
perinuclear region of cytoplasmVasopressin V2 receptorHomo sapiens (human)
plasma membraneVasopressin V2 receptorHomo sapiens (human)
endosomeVasopressin V1a receptorHomo sapiens (human)
plasma membraneVasopressin V1a receptorHomo sapiens (human)
endocytic vesicleVasopressin V1a receptorHomo sapiens (human)
plasma membraneVasopressin V1a receptorHomo sapiens (human)
virion membraneSpike glycoproteinSevere acute respiratory syndrome-related coronavirus
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (69)

Assay IDTitleYearJournalArticle
AID1745845Primary qHTS for Inhibitors of ATXN expression
AID1347089qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347099qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1347105qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347098qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347092qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347154Primary screen GU AMC qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1508630Primary qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome: Secreted ER Calcium Modulated Protein (SERCaMP) assay2021Cell reports, 04-27, Volume: 35, Issue:4
A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome.
AID1347102qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347086qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lymphocytic Choriomeningitis Arenaviruses (LCMV): LCMV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347094qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347096qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347083qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: Viability assay - alamar blue signal for LASV Primary Screen2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347103qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347101qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347090qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1347082qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: LASV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347095qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347097qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347091qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347107qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347108qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347100qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347093qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347104qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347106qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID483982Displacement [3H]Arg human recombinant Vasopressin V2 receptor2010Bioorganic & medicinal chemistry letters, Jun-15, Volume: 20, Issue:12
Synthesis and evaluation of azabicyclo[3.2.1]octane derivatives as potent mixed vasopressin antagonists.
AID444054Oral bioavailability in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1474166Liver toxicity in human assessed as induction of drug-induced liver injury by measuring severity class index2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID483983Selectivity ratio of Ki for human Vasopressin V1a receptor to Ki for human Vasopressin V2 receptor2010Bioorganic & medicinal chemistry letters, Jun-15, Volume: 20, Issue:12
Synthesis and evaluation of azabicyclo[3.2.1]octane derivatives as potent mixed vasopressin antagonists.
AID540212Mean residence time in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID444057Fraction escaping hepatic elimination in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID483986Selectivity ratio of IC50 for human Vasopressin V1a receptor to IC50 for human Vasopressin V2 receptor2010Bioorganic & medicinal chemistry letters, Jun-15, Volume: 20, Issue:12
Synthesis and evaluation of azabicyclo[3.2.1]octane derivatives as potent mixed vasopressin antagonists.
AID444051Total clearance in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID540210Clearance in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID444056Fraction escaping gut-wall elimination in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1386889Displacement of [3H]OT from OTR in Wistar rat uterus membranes incubated for 60 mins by microplate scintillation counting method2018Journal of medicinal chemistry, 10-11, Volume: 61, Issue:19
LIT-001, the First Nonpeptide Oxytocin Receptor Agonist that Improves Social Interaction in a Mouse Model of Autism.
AID483990Inhibition of CYP3A4 at 3 uM2010Bioorganic & medicinal chemistry letters, Jun-15, Volume: 20, Issue:12
Synthesis and evaluation of azabicyclo[3.2.1]octane derivatives as potent mixed vasopressin antagonists.
AID540209Volume of distribution at steady state in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID483992Inhibition of CYP2C9 at 3 uM2010Bioorganic & medicinal chemistry letters, Jun-15, Volume: 20, Issue:12
Synthesis and evaluation of azabicyclo[3.2.1]octane derivatives as potent mixed vasopressin antagonists.
AID444050Fraction unbound in human plasma2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1203551Potentiation of human GlyR-alpha1 expressed in Xenopus laevis oocytes assessed as induction of glycine-activated currents at 10 uM after 1 to 4 days by two-electrode voltage clamp assay relative to control2015Journal of medicinal chemistry, Apr-09, Volume: 58, Issue:7
Ensemble-based virtual screening for cannabinoid-like potentiators of the human glycine receptor α1 for the treatment of pain.
AID540211Fraction unbound in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID444053Renal clearance in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1386888Displacement of [3H]AVP from V2 receptor in Wistar rat kidney membranes incubated for 60 mins by microplate scintillation counting method2018Journal of medicinal chemistry, 10-11, Volume: 61, Issue:19
LIT-001, the First Nonpeptide Oxytocin Receptor Agonist that Improves Social Interaction in a Mouse Model of Autism.
AID1474167Liver toxicity in human assessed as induction of drug-induced liver injury by measuring verified drug-induced liver injury concern status2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID483984Antagonist activity at human Vasopressin V1a receptor assessed as inhibition of intracellular calcium mobilization by FLIPR assay2010Bioorganic & medicinal chemistry letters, Jun-15, Volume: 20, Issue:12
Synthesis and evaluation of azabicyclo[3.2.1]octane derivatives as potent mixed vasopressin antagonists.
AID483989Solubility of the compound2010Bioorganic & medicinal chemistry letters, Jun-15, Volume: 20, Issue:12
Synthesis and evaluation of azabicyclo[3.2.1]octane derivatives as potent mixed vasopressin antagonists.
AID483987Half life in human liver microsome at 1 uM2010Bioorganic & medicinal chemistry letters, Jun-15, Volume: 20, Issue:12
Synthesis and evaluation of azabicyclo[3.2.1]octane derivatives as potent mixed vasopressin antagonists.
AID1386887Displacement of [3H]AVP from V1B receptor in Wistar rat pituitary membranes incubated for 60 mins by microplate scintillation counting method2018Journal of medicinal chemistry, 10-11, Volume: 61, Issue:19
LIT-001, the First Nonpeptide Oxytocin Receptor Agonist that Improves Social Interaction in a Mouse Model of Autism.
AID483981Displacement [3H]Arg human recombinant Vasopressin V1a receptor2010Bioorganic & medicinal chemistry letters, Jun-15, Volume: 20, Issue:12
Synthesis and evaluation of azabicyclo[3.2.1]octane derivatives as potent mixed vasopressin antagonists.
AID483988Half life in mouse liver microsome at 1 uM2010Bioorganic & medicinal chemistry letters, Jun-15, Volume: 20, Issue:12
Synthesis and evaluation of azabicyclo[3.2.1]octane derivatives as potent mixed vasopressin antagonists.
AID483991Inhibition of CYP2D6 at 3 uM2010Bioorganic & medicinal chemistry letters, Jun-15, Volume: 20, Issue:12
Synthesis and evaluation of azabicyclo[3.2.1]octane derivatives as potent mixed vasopressin antagonists.
AID1203549Potentiation of human GlyR-alpha1 expressed in Xenopus laevis oocytes assessed as induction of glycine-activated currents at 1 uM after 1 to 4 days by two-electrode voltage clamp assay relative to control2015Journal of medicinal chemistry, Apr-09, Volume: 58, Issue:7
Ensemble-based virtual screening for cannabinoid-like potentiators of the human glycine receptor α1 for the treatment of pain.
AID444058Volume of distribution at steady state in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1386886Displacement of [3H]AVP from V1A receptor in Wistar rat liver membranes incubated for 60 mins by microplate scintillation counting method2018Journal of medicinal chemistry, 10-11, Volume: 61, Issue:19
LIT-001, the First Nonpeptide Oxytocin Receptor Agonist that Improves Social Interaction in a Mouse Model of Autism.
AID444052Hepatic clearance in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID483985Antagonist activity at human Vasopressin 2 receptor assessed as inhibition of intracellular cAMP accumulation2010Bioorganic & medicinal chemistry letters, Jun-15, Volume: 20, Issue:12
Synthesis and evaluation of azabicyclo[3.2.1]octane derivatives as potent mixed vasopressin antagonists.
AID540213Half life in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID444055Fraction absorbed in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1347160Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347159Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347411qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Mechanism Interrogation Plate v5.0 (MIPE) Libary2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1346432Human V1A receptor (Vasopressin and oxytocin receptors)1998Naunyn-Schmiedeberg's archives of pharmacology, Jan, Volume: 357, Issue:1
Pharmacological characterization of YM087, a potent, nonpeptide human vasopressin V1A and V2 receptor antagonist.
AID1346453Human V2 receptor (Vasopressin and oxytocin receptors)2010Bioorganic & medicinal chemistry letters, Jun-15, Volume: 20, Issue:12
Synthesis and evaluation of azabicyclo[3.2.1]octane derivatives as potent mixed vasopressin antagonists.
AID1346432Human V1A receptor (Vasopressin and oxytocin receptors)1998British journal of pharmacology, Dec, Volume: 125, Issue:7
Pharmacological characterization of the human vasopressin receptor subtypes stably expressed in Chinese hamster ovary cells.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (178)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's12 (6.74)18.2507
2000's84 (47.19)29.6817
2010's71 (39.89)24.3611
2020's11 (6.18)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 52.76

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index52.76 (24.57)
Research Supply Index5.33 (2.92)
Research Growth Index5.18 (4.65)
Search Engine Demand Index83.53 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (52.76)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials17 (9.04%)5.53%
Reviews78 (41.49%)6.00%
Case Studies13 (6.91%)4.05%
Observational0 (0.00%)0.25%
Other80 (42.55%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (21)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Phase 1, Open-Label Study to Assess the Effect of Severe Hepatic Impairment on the Pharmacokinetics of Intravenous Conivaptan [NCT01370148]Phase 117 participants (Actual)Interventional2011-04-30Completed
Open Label Study of the Safety and Efficacy of Conivaptan (Vaprisol®) to Raise Serum Sodium Levels in Patients With Severe Traumatic Brain Injury [NCT00930202]Phase 110 participants (Anticipated)Interventional2009-08-31Completed
A Phase 1, Open-Label Study to Assess the Effect of Hepatic Impairment on the Pharmacokinetics of Intravenous Conivaptan [NCT00851227]Phase 126 participants (Actual)Interventional2009-02-28Completed
A Phase 1, Open-Label Study to Assess the Effects of Renal Impairment on the Pharmacokinetics of Intravenous Conivaptan [NCT00887627]Phase 125 participants (Actual)Interventional2009-04-30Completed
Safety and Efficacy of Conivaptan for the Correction of Euvolemic and Hypervolemic Hyponatremia in Critically Ill Neurological Patients [NCT00684164]Phase 30 participants (Actual)Interventional2008-05-31Withdrawn(stopped due to Unable to complete a contract with the Sponsor)
Use of Conivaptan (Vaprisol) for Hyponatremic Neuro-ICU Patients [NCT00727090]Phase 46 participants (Actual)Interventional2008-08-31Terminated(stopped due to Enrollment below goal.)
Evaluation of the Diuretic and Renal Effects of Vaprisol When Administered Along With Furosemide and Nesiritide Continuous Infusion [NCT00806910]Phase 40 participants (Actual)Interventional2008-10-31Withdrawn(stopped due to Sponsor support withdrawn)
Treatment of Brain Edema and Herniation Secondary to Ischemic or Hemorrhagic Stroke [NCT01954290]Phase 20 participants (Actual)Interventional2015-09-30Withdrawn(stopped due to Investigator is leaving the institution.)
Body Volume Regulation in Pulmonary Arterial Hypertension With Right Ventricular Failure [NCT00811486]0 participants (Actual)Interventional2009-01-31Withdrawn(stopped due to Only 1 patient recruited, and he withdrew)
Comparative Effects of Conivaptan and Loop Diuretics on Plasma Neurohormones and Systemic and Renal Hemodynamics in Subjects With Chronic Congestive Heart Failure [NCT00924014]8 participants (Anticipated)Interventional2009-07-31Not yet recruiting
Effects on Exercise Hemodynamics of Vasopressin Blockade by Conivaptan Infusion in Heart Failure Patients [NCT01752543]Phase 420 participants (Actual)Interventional2013-12-31Completed
A 5-Day, Double-Blind, Placebo-Controlled Multicenter Study of Oral YM087 (CI-1025) to Assess Efficacy and Safety in Patients With Euvolemic or Hypervolemic Hyponatremia [NCT00492037]Phase 383 participants (Actual)Interventional2000-01-31Completed
A Randomized, Double-blind, Placebo-controlled, Dose-ranging Pilot Study Evaluating the Efficacy and Safety of YM087 in Patients With Decompensated Chronic Heart Failure [NCT00057356]Phase 2170 participants (Actual)Interventional2002-11-30Completed
A Phase 2, Randomized, Double Blind, Placebo Controlled, Dose Escalation Study to Assess the Safety and Effects of Intravenous Conivaptan on the Hepatic Hemodynamic Response in Stable Euvolemic or Hypervolemic Cirrhotic Patients [NCT00592475]Phase 220 participants (Actual)Interventional2007-12-31Completed
A 4-Day, Double-Blind, Placebo-Controlled, Multicenter Study of IV YM087 (CI-1025) to Assess Efficacy and Safety in Patients With Euvolemic or Hypervolemic Hyponatremia [NCT00380575]Phase 384 participants Interventional2000-08-31Completed
A 4-day, Open-Label, Multicenter Phase 3b Study of IV YM087 in Patients With Euvolemic or Hypervolemic Hyponatremia [NCT00379847]Phase 3251 participants (Actual)Interventional2004-02-29Completed
Conivaptan for the Reduction of Cerebral Edema in Intracerebral Hemorrhage- A Safety and Tolerability Study [NCT03000283]Phase 17 participants (Actual)Interventional2017-03-22Completed
A Phase-3b, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Assess the Safety and Efficacy of Conivaptan in Symptomatic Acute Decompensated Heart Failure (ADHF) Subjects With Hyponatremia [NCT00843986]Phase 39 participants (Actual)Interventional2009-04-30Terminated(stopped due to The clinical study has been terminated based on difficulties to enroll eligible subjects per protocol inclusion and exclusion criteria.)
A Phase 4, Randomized, Parallel Group, Multi-Center Study to Assess the Safety and Efficacy of Multiple Dosing Regimens of IV Conivaptan in Subjects With Euvolemic or Hypervolemic Hyponatremia [NCT00435591]Phase 4121 participants (Actual)Interventional2007-01-31Completed
A Phase III, Double-Blind, Randomized, Placebo-Controlled, Multi-Center, Dose-Titration Study to Assess the Efficacy, Safety and Pharmacokinetics of Intravenous Conivaptan (Vaprisol®) in Pediatric Subjects With Euvolemic or Hypervolemic Hyponatremia [NCT01451411]Phase 34 participants (Actual)Interventional2012-02-29Terminated(stopped due to Enrollment goals were not met.)
A Phase IIIb, Randomized, Double-Blind, Parallel Group, Multi-Center, Study to Assess the Efficacy and Safety of Multiple 30 Minute Infusions of YM087 (Conivaptan) in Subjects With Euvolemic or Hypervolemic Hyponatremia [NCT00478192]Phase 350 participants (Actual)Interventional2007-04-30Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00435591 (6) [back to overview]Number of Patients With Confirmed Serum Sodium Level Exceeding 4 mEq/L Increase From Baseline Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours
NCT00435591 (6) [back to overview]Number and Severity of Infusion Site Reactions (ISRs) Using a Modified ISR Reporting Scale for Phlebitis and Infiltration in Patients Treated With Dose Regimen 1 and Dose Regimen 2
NCT00435591 (6) [back to overview]Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period
NCT00435591 (6) [back to overview]Baseline Adjusted Area Under the Concentration - Time Curve (AUC) in Serum Sodium Over the Duration of the First 24.5 Hours, the First 48.5 Hours, and the First 96.5 Hours
NCT00435591 (6) [back to overview]Time From the First Dose of Study Drug to a Confirmed > 4 mEq/L Increase From Baseline in Serum Sodium During the 48.5 Hour Treatment Period
NCT00435591 (6) [back to overview]Number of Patients With Confirmed Serum Sodium Level Exceeding 6 mEq/L Increase From Baseline or Confirmed Normal Serum Sodium Level Exceeding 135 mEq/L Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours
NCT00478192 (8) [back to overview]Change in Serum Sodium From Baseline to the 48 Hour Assessment or Study Drug Discontinuation.
NCT00478192 (8) [back to overview]Baseline -Adjusted Area Under the Curve (AUC) in Serum Sodium Over the Duration 0 to 48 Hours
NCT00478192 (8) [back to overview]Number of Patients With Confirmed Serum Sodium Level > 4 mEq/L Increase From Baseline Over 0 to 48 Hours
NCT00478192 (8) [back to overview]Number of Patients With Confirmed Serum Sodium Level Increase >6 mEq/L From Baseline or Confirmed Normal Serum Sodium Level (>135 mEq/L) Over the Duration 0 to 48 Hours
NCT00478192 (8) [back to overview]Time From the First Dose of Study Medication to a Confirmed >4 mEq/L Increase From Baseline in Serum Sodium
NCT00478192 (8) [back to overview]Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment
NCT00478192 (8) [back to overview]Change From Baseline in Free Water Clearance (FWC) at Each Time Point Through the 48-hour Assessment
NCT00478192 (8) [back to overview]Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment
NCT00592475 (6) [back to overview]Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at 0.5, 1, and 1.5 Hours Post Dose
NCT00592475 (6) [back to overview]Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose
NCT00592475 (6) [back to overview]Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose
NCT00592475 (6) [back to overview]Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose
NCT00592475 (6) [back to overview]Change From Baseline in Hepatic Blood Flow (HBF) at 0.5, 1, and 1.5 Hours Post Dose
NCT00592475 (6) [back to overview]Change From Baseline in Hepatic Mean Arterial Pressure (MAP) at 0.5, 1, and 1.5 Hours Post Dose
NCT00727090 (8) [back to overview]Change in Serum Sodium From Baseline to 18 Hours
NCT00727090 (8) [back to overview]Change in Serum Sodium From Baseline to 24 Hours
NCT00727090 (8) [back to overview]Change in Serum Sodium From Baseline to 36 Hours
NCT00727090 (8) [back to overview]Change in Serum Sodium From Baseline to 48 Hours
NCT00727090 (8) [back to overview]Change in Serum Sodium From Baseline to 6 Hours
NCT00727090 (8) [back to overview]Glasgow Coma Scale
NCT00727090 (8) [back to overview]NIH Stroke Scale
NCT00727090 (8) [back to overview]Change in Serum Sodium From Baseline to 12 Hours
NCT01451411 (5) [back to overview]Number of Patients With Confirmed ≥ 4 mEq/L Increase From Baseline in Serum Sodium
NCT01451411 (5) [back to overview]Number of Subjects With Confirmed > 6 mEq/L Increase From Baseline in Serum Sodium or a Confirmed Normal Serum Sodium Level (Greater Than or Equal to 135 mEq/L)
NCT01451411 (5) [back to overview]Time From the First Dose of Study Medication to a Confirmed ≥ 4 mEq/L Increase From Baseline in Serum Sodium
NCT01451411 (5) [back to overview]Mean Change From Baseline to the End of the 48-hour Treatment Period in Serum Sodium
NCT01451411 (5) [back to overview]Number of Participants With an Overly Rapid Rise in Serum Sodium From Baseline
NCT03000283 (6) [back to overview]Modified Rankin Scale (mRS) Score
NCT03000283 (6) [back to overview]In-hospital Mortality
NCT03000283 (6) [back to overview]Cost
NCT03000283 (6) [back to overview]Change in Cerebral Edema
NCT03000283 (6) [back to overview]Cost
NCT03000283 (6) [back to overview]Patient Tolerance of Conivaptan

Number of Patients With Confirmed Serum Sodium Level Exceeding 4 mEq/L Increase From Baseline Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours

"Patients with confirmed serum sodium level exceeding 4 mEq/L increase from baseline.~Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period." (NCT00435591)
Timeframe: 0-24.5 hours, 0-48.5 hours and 0-96.5 hours

,,,
InterventionParticipants (Number)
0 - 24.5 Hours0 - 48.5 Hours0 - 96.5 Hours
Dose Regimen 161321
Dose Regimen 2131522
Dose Regimen 3132327
Dose Regimen 4101924

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Number and Severity of Infusion Site Reactions (ISRs) Using a Modified ISR Reporting Scale for Phlebitis and Infiltration in Patients Treated With Dose Regimen 1 and Dose Regimen 2

"Infusion Site Reaction (ISR) was any local event other than isolated pain, bleeding, or bruising at the site of infusion.~One ISRMS has been reported for each participant & represents the most severe state of ISR for that participant.~ISR scale is a health care provider assessment of ISRs using the following modified 5 point reporting scale: 0= No new reaction; 1+=Infusion site erythema, infusion site pain, infusion site warmth; 2+= Infusion site edema; 3+=Phlebitis, venous induration; 4+=Thrombophlebitis, venous thrombosis, infusion site infection, infusion site cellulitis" (NCT00435591)
Timeframe: 48 hours

,
InterventionParticipants (Number)
Infusion Site Reaction - No assessmentInfusion Site Reaction - 0Infusion Site Reaction - 1+Infusion Site Reaction - 2+Infusion Site Reaction - 3+Infusion Site Reaction - 4+
Dose Regimen 10175240
Dose Regimen 21167051

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Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period

"Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period.~Change from Baseline is calculated as Time point minus Baseline." (NCT00435591)
Timeframe: Baseline at 4, 6, 10, 16, 24, 30, 40, 48.5 hours and 7 days post-treatment

,,,
Interventionmmol/L (Mean)
BaselineChange at Hour 4 (N=28; 26; 30; 28)Change at Hour 6 (N=27; 27; 29; 27)Change at Hour 10 (N=27; 28; 30; 26)Change at Hour 16 (N=24; 24; 27; 23)Change at Hour 24 (N= 27; 27; 30; 24)Change at Hour 30 (N=27; 28; 28; 23)Change at Hour 40 (N=24; 26; 26; 24)Change at Hour 48.5 (N=26; 28; 28; 27)Change at Day 7 (N=23; 27; 25; 17)
Dose Regimen 1124.61.21.12.32.03.33.14.34.66.7
Dose Regimen 2123.51.52.52.94.04.54.55.15.89.6
Dose Regimen 3124.50.71.52.74.24.44.86.96.57.2
Dose Regimen 4124.01.92.72.94.85.04.16.15.48.9

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Baseline Adjusted Area Under the Concentration - Time Curve (AUC) in Serum Sodium Over the Duration of the First 24.5 Hours, the First 48.5 Hours, and the First 96.5 Hours

"AUCna t is calculated as the baseline-adjusted area under serum sodium levels for a duration of time 0 to time t.~Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period." (NCT00435591)
Timeframe: 24.5 hours, 48.5 hours and 96.5 hours

,,,
Interventionhr * mEq/L (Mean)
AUCna at 24.5 hoursAUCna at 48.5 hoursAUCna at 96.5 hours
Dose Regimen 145.600133.664375.379
Dose Regimen 270.569194.561503.127
Dose Regimen 366.096205.522558.926
Dose Regimen 482.470207.043528.377

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Time From the First Dose of Study Drug to a Confirmed > 4 mEq/L Increase From Baseline in Serum Sodium During the 48.5 Hour Treatment Period

"The upper limits of the interquartile range were not estimable in three of the treatment arms. Only the placebo loading dose + YM087 premix continuous infusion arm will be reported.~Time is number of hours to reach an increase of exceeding 4 mEq/L from baseline serum sodium.~Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period." (NCT00435591)
Timeframe: 48.5 hours

InterventionHours (Median)
Dose Regimen 324.08

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Number of Patients With Confirmed Serum Sodium Level Exceeding 6 mEq/L Increase From Baseline or Confirmed Normal Serum Sodium Level Exceeding 135 mEq/L Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours

"Patients with confirmed serum sodium level exceeding 6 mEq/L increase from baseline or confirmed normal serum sodium level exceeding 135 mEq/L.~Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period." (NCT00435591)
Timeframe: 0-24.5 hours, 0-48.5 hours and 0-96.5 hours

,,,
InterventionParticipants (Number)
0 - 24.5 Hours0 - 48.5 Hours0 - 96.5 Hours
Dose Regimen 11613
Dose Regimen 261316
Dose Regimen 371724
Dose Regimen 461219

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Change in Serum Sodium From Baseline to the 48 Hour Assessment or Study Drug Discontinuation.

"Baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1.~Hour 48: Hour 48 or time that ended study participation prior to the hour 48 assessment.~Change is calculated as Hour 48 - Baseline." (NCT00478192)
Timeframe: Baseline and 48 hours

,,
InterventionmEq/L (Mean)
Baseline (N= 20; 20; 9)Hour 48 (N=19; 17; 8)Change from Baseline (N=19; 17; 8)
Regimen 1 Conivaptan QD126.03130.44.00
Regimen 2 Conivaptan BID126.39133.47.36
Regimen 3 Placebo125.55127.61.16

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Baseline -Adjusted Area Under the Curve (AUC) in Serum Sodium Over the Duration 0 to 48 Hours

"Each individual subject's change from baseline serum sodium levels was used to calculate baseline adjusted area under the curve serum sodium levels for a duration of Time 0 to Time t in hours (labeled as AUC(Na)(0-t). The last available serum sodium level prior to dosing on Day 1 was used as baseline.~t=48 Hours" (NCT00478192)
Timeframe: 48 Hours

InterventionHour * mEq/L (Mean)
Regimen 1 Conivaptan QD142.72
Regimen 2 Conivaptan BID244.17
Regimen 3 Placebo23.21

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Number of Patients With Confirmed Serum Sodium Level > 4 mEq/L Increase From Baseline Over 0 to 48 Hours

Confirmed sodium levels refers to two consecutive increases from baseline in sodium of >4 mEq/L; baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1. (NCT00478192)
Timeframe: 48 Hours

InterventionPatients (Number)
Regimen 1 Conivaptan QD12
Regimen 2 Conivaptan BID17
Regimen 3 Placebo2

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Number of Patients With Confirmed Serum Sodium Level Increase >6 mEq/L From Baseline or Confirmed Normal Serum Sodium Level (>135 mEq/L) Over the Duration 0 to 48 Hours

Confirmed sodium levels refers to two consecutive increases from baseline in sodium of >6 mEq/L or two consecutive measurements >135 mEq/L; baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1. (NCT00478192)
Timeframe: 48 Hours

InterventionPatients (Number)
Regimen 1 Conivaptan QD6
Regimen 2 Conivaptan BID11
Regimen 3 Placebo0

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Time From the First Dose of Study Medication to a Confirmed >4 mEq/L Increase From Baseline in Serum Sodium

"Confirmed sodium levels refers to two consecutive increases from baseline in sodium of >4 mEq/L; baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1.~The endpoint was not evaluable in the placebo arm (median and interquartile range cannot be estimated) or the conivaptan QD arm (interquartile range cannot be estimated) because too high a percentage of patients were censored for the event. Only the conivaptan BID arm will be reported." (NCT00478192)
Timeframe: 48 Hours

InterventionHours (Median)
Regimen 2 Conivaptan BID16.43

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Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment

"Effective water clearence (EWC) was calculated as EWC=V(1-(Una+Uk)/(Pna+Pk)), where V is urine volume, Una is the urine sodium concentration, Uk is the urine potassium concentration, Pna is the serum/plasma sodium concentration, an Pk is the serum /plasma potassium concentration.~Baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1.~Hour 48: Hour 48 or time that ended study participation prior to the hour 48 assessment.~Change is calculated as Actual Data for each time point - Baseline" (NCT00478192)
Timeframe: Baseline, Hour 12, Hour 24,Hour 36 and Hour 48

,,
InterventionmL (Mean)
Baseline (N=16; 12; 6)Hour 12 (N=14; 12; 5)Change at Hour 12 (N=12;12; 4)Hour 24 (N=14; 12; 6)Change at Hour 24 (N=13; 11; 5)Hour 36 (N=15; 11; 6)Change at Hour 36 (N=12; 8; 5)Hour 48 (N=14; 11; 5)Change at Hour 48 (N=12; 10; 4)
Regimen 1 Conivaptan QD6.76355.65301.52-50.19-70.6136.85-91.07-77.3780.23
Regimen 2 Conivaptan BID39.86405.21365.35-261.27-391.7612.66-89.12-179.37-240.39
Regimen 3 Placebo18.66136.22135.44368.01383.73726.96810.45569.09690.98

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Change From Baseline in Free Water Clearance (FWC) at Each Time Point Through the 48-hour Assessment

"Free water clearance (FWC) was calculated as FWC=V(1-Uosm/Posm), where V is urine volume, Uosm is the urine osmolality, Posm is the plasma sodium osmolality.~Baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1.~Hour 48: Hour 48 or time that ended study participation prior to the hour 48 assessment.~Change is calculated as Actual Data for each time point - Baseline" (NCT00478192)
Timeframe: Baseline, Hour 24 and Hour 48

,,
InterventionmL (Mean)
Baseline (N=14; 11; 6)Hour 24 (N=14; 12; 6)Change at Hour 24 (N=11; 10; 5)Hour 48 (N=14;12; 5)Change at Hour 48 (N=11; 10; 4)
Regimen 1 Conivaptan QD-53.87-972.29-936.99-1243.39-1313.98
Regimen 2 Conivaptan BID6.55-611.14-513.33-769.19-603.67
Regimen 3 Placebo-34.90-416.71-420.75-592.96-702.11

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Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment

"Baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1.~Hour 48: Hour 48 or time that ended study participation prior to the hour 48 assessment.~Change is calculated as Actual Data for each time point - Baseline" (NCT00478192)
Timeframe: Baseline, Hour 4, Hour 12, Hour 16, Hour 24, Hour 28, Hour 36, Hour 40 and Hour 48

,,
InterventionmEq/L (Mean)
Baseline (N=20; 20; 9)Hour 4 (N=19; 20; 8)Change at Hour 4 (N=19; 20; 8)Hour 12 (N=19; 19; 7)Change at Hour 12 (N=19; 19; 7)Hour 16 (N=19; 17; 7)Change at Hour 16 (N=19; 17; 7)Hour 24 (N=18; 16; 8)Change at Hour 24 (N=18; 16; 8)Hour 28 (N=19; 17; 8)Change at Hour 28 (N=19; 17; 8)Hour 36 (N=19; 15; 8)Change at Hour 36 (N=19; 15; 8)Hour 40 (N=19; 16; 8)Change at Hour 40 (N=19; 16; 8)Hour 48 (N=19; 17; 8)Change at Hour 48 (N=19; 17; 8)
Regimen 1 Conivaptan QD126.03128.031.59128.221.78129.342.90128.872.66130.794.35131.424.98130.834.39130.444.00
Regimen 2 Conivaptan BID126.39128.472.08130.854.65131.044.93130.744.62131.625.51132.476.54132.236.30133.357.36
Regimen 3 Placebo125.55125.80-0.63127.210.73127.571.09127.481.05126.490.06127.310.89127.000.58127.591.16

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Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at 0.5, 1, and 1.5 Hours Post Dose

"Change from baseline is calculated as time point minus baseline.~Baseline procedures were performed prior to study drug administration." (NCT00592475)
Timeframe: Baseline and 0.5, 1, and 1.5 hours post dose

,,
InterventionmmHg (Mean)
BaselineChange at 0.5 HoursChange at 1 HourChange at 1.5 Hours
Regimen 1 Conivaptan 12.5 mg16.580.330.500.83
Regimen 2 Conivaptan 25 mg18.330.110.560.83
Regimen 3 Placebo15.80-0.10-0.60-0.10

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Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose

"Baseline serum sodium value is the last measurement prior to dosing.~Change from baseline is calculated as time point minus baseline." (NCT00592475)
Timeframe: Baseline and 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 hours and on Day 8 post dose

,,
InterventionmEq/L (Mean)
Baseline (N= 6; 9; 5)Change at 0.5 Hours (N= 6; 9; 5)Change at 1 Hour (N= 6; 9; 5)Change at 2.5 Hours (N= 6; 9; 5)Change at 4 Hours (N= 6; 9; 5)Change at 6.5 Hours (N= 6; 9; 5)Change at 9 Hours (N= 5; 9; 5)Change at 12 Hours (N= 6; 9; 5)Change at 24 Hours (N= 6; 9; 5)Change at 8 Days (N= 6; 9; 5)
Regimen 1 Conivaptan 12.5 mg137.3-1.3-0.31.8-2.2-1.2-2.6-3.7-1.5-2.3
Regimen 2 Conivaptan 25 mg137.1-1.10.90.2-1.01.30.80.10.10.1
Regimen 3 Placebo131.2-0.8-1.80.0-3.6-2.4-2.4-2.2-2.02.0

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Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose

"Change from baseline is calculated as time point minus baseline.~Baseline procedures were performed prior to study drug administration." (NCT00592475)
Timeframe: Baseline and 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 hours, and Day 8 post dose

,,
InterventionmmHg (Mean)
Systolic Blood Pressure- BaselineSystolic Blood Pressure- Change at 0.5 HoursSystolic Blood Pressure- Change at 1 HourSystolic Blood Pressure- Change at 1.5 HoursSystolic Blood Pressure- Change at 2.5 HoursSystolic Blood Pressure- Change at 3.5 HoursSystolic Blood Pressure- Change at 4.5 HoursSystolic Blood Pressure- Change at 5.5 HoursSystolic Blood Pressure- Change at 6.5 HoursSystolic Blood Pressure- Change at 9 HoursSystolic Blood Pressure- Change at 12 HoursSystolic Blood Pressure- Change at 24 HoursSystolic Blood Pressure- Change at 8 DaysDiastolic Blood Pressure- BaselineDiastolic Blood Pressure- Change at 0.5 HoursDiastolic Blood Pressure- Change at 1 HourDiastolic Blood Pressure- Change at 1.5 HoursDiastolic Blood Pressure- Change at 2.5 HoursDiastolic Blood Pressure- Change at 3.5 HoursDiastolic Blood Pressure- Change at 4.5 HoursDiastolic Blood Pressure- Change at 5.5 HoursDiastolic Blood Pressure- Change at 6.5 HoursDiastolic Blood Pressure- Change at 9 HoursDiastolic Blood Pressure- Change at 12 HoursDiastolic Blood Pressure- Change at 24 HoursDiastolic Blood Pressure- Change at 8 Days
Regimen 1 Conivaptan 12.5 mg112.25.35.57.8-2.5-6.0-6.2-6.3-8.8-5.5-14.0-10.8-11.560.34.57.39.22.21.0-2.52.7-1.05.00.0-0.5-3.0
Regimen 2 Conivaptan 25 mg115.05.213.97.2-3.8-6.3-17.1-8.7-9.71.9-7.8-7.8-7.866.34.95.15.7-2.1-0.9-6.3-4.2-4.70.3-3.3-5.1-5.0
Regimen 3 Placebo112.812.86.81.2-2.6-11.4-8.2-7.6-9.4-7.2-5.8-11.0-5.471.61.83.64.0-3.2-6.8-6.4-9.8-7.6-4.4-6.0-11.4-7.6

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Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose

"Change from baseline is calculated as time point minus baseline.~Baseline procedures were performed prior to study drug administration." (NCT00592475)
Timeframe: Baseline and 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 hours, and Day 8 post dose

,,
Interventionbpm (Mean)
BaselineChange at 0.5 HoursChange at 1 HourChange at 1.5 HoursChange at 2.5 HoursChange at 3.5 HoursChange at 4.5 HoursChange at 5.5 HoursChange at 6.5 HoursChange at 9 HoursChange at 12 HoursChange at 24 HoursChange at 8 Days
Regimen 1 Conivaptan 12.5 mg69.00.73.02.3-0.31.33.34.38.04.81.81.20.7
Regimen 2 Conivaptan 25 mg77.3-6.0-5.4-4.0-8.6-1.4-1.2-2.9-4.0-0.99.02.7-7.1
Regimen 3 Placebo72.0-2.0-2.4-3.20.42.84.03.63.41.83.83.6-0.8

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Change From Baseline in Hepatic Blood Flow (HBF) at 0.5, 1, and 1.5 Hours Post Dose

"Change from baseline is calculated as time point minus baseline.~Baseline procedures were performed prior to study drug administration." (NCT00592475)
Timeframe: Baseline and 0.5, 1, and 1.5 hours post dose

,,
InterventionmL/min (Mean)
Baseline (N= 4; 9; 5)Change at 0.5 Hours (N= 4; 9; 5)Change at 1 Hour (N= 4; 9; 4)Change at 1.5 Hours (N= 4; 9; 5)
Regimen 1 Conivaptan 12.5 mg581.053.51.315.8
Regimen 2 Conivaptan 25 mg1182.2-74.1-70.0-96.0
Regimen 3 Placebo649.673.8-67.540.8

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Change From Baseline in Hepatic Mean Arterial Pressure (MAP) at 0.5, 1, and 1.5 Hours Post Dose

"Change from baseline is calculated as time point minus baseline.~Baseline procedures were performed prior to study drug administration." (NCT00592475)
Timeframe: Baseline and 0.5, 1, and 1.5 hours post dose

,,
InterventionmmHg (Mean)
Baseline (N= 6; 9; 5)Change at 0.5 Hours (N= 6; 8; 5)Change at 1.0 Hour (N= 6; 9; 5)Change at 1.5 Hours (N= 6; 9; 5)
Regimen 1 Conivaptan 12.5 mg88.3-6.2-4.20
Regimen 2 Conivaptan 25 mg90.33.65.78.8
Regimen 3 Placebo84.62.67.83.4

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Change in Serum Sodium From Baseline to 18 Hours

(NCT00727090)
Timeframe: 18 hours

InterventionmMol/L (Mean)
Treatment: Conivaptan7.3
Usual Medical Care1.3

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Change in Serum Sodium From Baseline to 24 Hours

(NCT00727090)
Timeframe: 24 hours

InterventionmMol/L (Mean)
Treatment: Conivaptan9.7
Usual Medical Care0

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Change in Serum Sodium From Baseline to 36 Hours

(NCT00727090)
Timeframe: 36 hours

InterventionmMol/L (Mean)
Treatment: Conivaptan8
Usual Medical Care-1.7

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Change in Serum Sodium From Baseline to 48 Hours

(NCT00727090)
Timeframe: 48 hours

InterventionmMol/L (Mean)
Treatment: Conivaptan6
Usual Medical Care-0.7

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Change in Serum Sodium From Baseline to 6 Hours

(NCT00727090)
Timeframe: 48 hours

InterventionmMol/L (Mean)
Treatment: Conivaptan7
Usual Medical Care-0.6

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Glasgow Coma Scale

Standardized examination of mental status ranging from 3 (worst) to 15 (best possible) (NCT00727090)
Timeframe: 48 hours

Interventionscore on a scale (Median)
Conivaptan9
Usual Care12

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NIH Stroke Scale

Standardized neurologic examination, ranging from 0 (best) to 42 (worst possible). (NCT00727090)
Timeframe: 48 hours

Interventionscore on a scale (Median)
Conivaptan19
Usual Care12

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Change in Serum Sodium From Baseline to 12 Hours

(NCT00727090)
Timeframe: 12 hours

InterventionmMol/L (Mean)
Treatment: Conivaptan7.7
Usual Medical Care1.7

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Number of Patients With Confirmed ≥ 4 mEq/L Increase From Baseline in Serum Sodium

(NCT01451411)
Timeframe: baseline and 48 hours

Interventionparticipants (Number)
Conivaptan Hydrochloride2
Placebo0

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Number of Subjects With Confirmed > 6 mEq/L Increase From Baseline in Serum Sodium or a Confirmed Normal Serum Sodium Level (Greater Than or Equal to 135 mEq/L)

(NCT01451411)
Timeframe: baseline and 48 hours

Interventionparticipants (Number)
Conivaptan Hydrochloride1
Placebo0

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Time From the First Dose of Study Medication to a Confirmed ≥ 4 mEq/L Increase From Baseline in Serum Sodium

(NCT01451411)
Timeframe: 48 hours

Interventionhours (Mean)
Conivaptan Hydrochloride21.5

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Mean Change From Baseline to the End of the 48-hour Treatment Period in Serum Sodium

(NCT01451411)
Timeframe: baseline and 48 hours

InterventionmEq/L (Mean)
Conivaptan Hydrochloride6.0
Placebo-4.0

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Number of Participants With an Overly Rapid Rise in Serum Sodium From Baseline

an absolute serum sodium of 145 mEq/L at Hour 24 or an increase in serum sodium of greater than 12 mEq/L (NCT01451411)
Timeframe: baseline and Hours 3, 8, 12 and 24.

Interventionparticipants (Number)
Conivaptan Hydrochloride0
Placebo0

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Modified Rankin Scale (mRS) Score

Modified Rankin Scale (0 to 6) at discharge from the hospital. A score of 0 indicates no disability and a score of 6 indicates the patient died. Functional independence is defined as a score of 2 or less. (NCT03000283)
Timeframe: At discharge from ICU and from hospital, up to 3 weeks

Interventionscore on a scale (Median)
Conivaptan Treatment Group5

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In-hospital Mortality

All-cause deaths during hospitalization (NCT03000283)
Timeframe: Enrollment through hospital discharge, up to 3 weeks

InterventionParticipants (Count of Participants)
Conivaptan Treatment Group0

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Cost

Cost as measured by length of stay in the neuro ICU. (NCT03000283)
Timeframe: Enrollment through hospital discharge, up to 3 weeks

Interventiondays (Mean)
Conivaptan Treatment Group14.4

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Change in Cerebral Edema

Changes in cerebral edema (CE) as measured on CT. Goal is a -5 to -10% change in CE over time. Change will be measured both as absolute change in volume, calculated as the final volume minus the baseline volume measure and converted to a percentage of the baseline volume measure. (NCT03000283)
Timeframe: Baseline to 168 hours post-enrollment

Interventionpercentage of change from baseline (Mean)
Conivaptan Treatment Group-37.1

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Cost

"Cost as measured by:~Need for external ventricular drain (EVD)/bolt or surgical procedures (craniectomy, clot evacuation,VPS) for reduction/management of CE.~Need for central venous lines, arterial lines, peripherally inserted central venous catheter (PICC) lines, tracheostomy/percutaneous endoscopic gastrostomies (PEGs).~Number of patients requiring a ventilator." (NCT03000283)
Timeframe: Baseline to 168 hours post-enrollment

InterventionParticipants (Count of Participants)
EVD/bolt or surgical proceduresLines or tracheostomy/PEGVentilator
Conivaptan Treatment Group071

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Patient Tolerance of Conivaptan

The number of participants with abnormal seizure activity and/or abnormal lab values and/or increase in infection rate and/or any drug-related adverse events. (NCT03000283)
Timeframe: Baseline to 168 hours post-enrollment

InterventionParticipants (Count of Participants)
Abnormal Seizure ActivityAbnormal Lab ValuesInfectionsDrug-related Adverse Events
Conivaptan Treatment Group0010

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