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Details

Stereochemistry RACEMIC
Molecular Formula C26H25ClN2O3
Molecular Weight 448.941
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TOLVAPTAN

SMILES

CC1=CC=CC=C1C(=O)NC2=CC(C)=C(C=C2)C(=O)N3CCCC(O)C4=C3C=CC(Cl)=C4

InChI

InChIKey=GYHCTFXIZSNGJT-UHFFFAOYSA-N
InChI=1S/C26H25ClN2O3/c1-16-6-3-4-7-20(16)25(31)28-19-10-11-21(17(2)14-19)26(32)29-13-5-8-24(30)22-15-18(27)9-12-23(22)29/h3-4,6-7,9-12,14-15,24,30H,5,8,13H2,1-2H3,(H,28,31)

HIDE SMILES / InChI

Description

Tolvaptan is a selective and competitive arginine vasopressin receptor 2 antagonist. Vasopressin acts on the V2 receptors found in the walls of the vasculature and luminal membranes of renal collecting ducts. By blocking V2 receptors in the renal collecting ducts, aquaporins do not insert themselves into the walls thus preventing water absorption. This action ultimately results in an increase in urine volume, decrease urine osmolality, and increase electrolyte-free water clearance to reduce intravascular volume and an increase serum sodium levels. Tolvaptan is especially useful for heart failure patients as they have higher serum levels of vasopressin. Tolvaptan is used to treat low blood sodium levels (hyponatremia) associated with various conditions like congestive heart failure, cirrhosis, and syndrome of inappropriate antidiuretic hormones (SIADH). FDA approved on May 19, 2009. Tolvaptan is sold under the trade names Samsca and Jinarc.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
0.43 nM [Ki]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Samsca

Cmax

ValueDoseCo-administeredAnalytePopulation
198 ng/mL
30 mg 1 times / day multiple, oral
TOLVAPTAN blood
Homo sapiens
125 ng/mL
15 mg single, oral
TOLVAPTAN blood
Homo sapiens
154 ng/mL
15 mg single, oral
TOLVAPTAN blood
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
1193 ng × h/mL
30 mg 1 times / day multiple, oral
TOLVAPTAN blood
Homo sapiens
683 ng × h/mL
15 mg single, oral
TOLVAPTAN blood
Homo sapiens
719 ng × h/mL
15 mg single, oral
TOLVAPTAN blood
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
3.3 h
30 mg 1 times / day multiple, oral
TOLVAPTAN blood
Homo sapiens
3.5 h
15 mg single, oral
TOLVAPTAN blood
Homo sapiens
3.2 h
15 mg single, oral
TOLVAPTAN blood
Homo sapiens

Doses

AEs

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Patents

Sample Use Guides

In Vivo Use Guide
The usual starting dose for Samsca (Tolvaptan) is 15 mg administered once daily without regard to meals. Increase the dose to 30 mg once daily, after at least 24 hours, to a maximum of 60 mg once daily, as needed to achieve the desired level of serum sodium. Do not administer Samsca for more than 30 days to minimize the risk of liver injury
Route of Administration: Oral
In Vitro Use Guide
Tolvaptan caused a concentration-dependent inhibition of AVP-induced cAMP production with an apparent IC(50) of ∼10(-10) M.