Tolvaptan

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 Search

SMILES

CC1=CC=CC=C1C(=O)NC2=CC=C(C(=O)N3CCCC(O)C4=CC(Cl)=CC=C34)C(C)=C2

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

Molecular Formula	C26H25ClN2O3
Molecular Weight	448.941
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: http://www.drugbank.ca/drugs/DB06212
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/samsca.html

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 Target	Pharmacology	Condition	Potency
Vasopressin V2 receptor 16 Target ID: CHEMBL1790 Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=5526617c-c7b9-4556-886d-729bbabbc566&type=display	Antagonist 2849		0.43 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypervolemic and euvolemic hyponatremia 1 Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=5526617c-c7b9-4556-886d-729bbabbc566&type=display	Primary		Approved 8583	Samsca Approved Use Samsca® is indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia (serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure and Syndrome of Inappropriate Antidiuretic Hormone (SIADH). Launch Date 2009

C_max

Value	Dose	Analyte	Population
247.7 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22130104/	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLVAPTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
190.5 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22130104/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLVAPTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
125 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22120090	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLVAPTAN blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
154 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22120090	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLVAPTAN blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
198 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22120090	30 mg 1 times / day multiple, oral dose: 30 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TOLVAPTAN blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
1911.7 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22130104/	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLVAPTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1281.2 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22130104/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLVAPTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
683 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22120090	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLVAPTAN blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
719 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22120090	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLVAPTAN blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
1193 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22120090	30 mg 1 times / day multiple, oral dose: 30 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TOLVAPTAN blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
5.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22130104/	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLVAPTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22130104/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLVAPTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3.5 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22120090	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLVAPTAN blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3.2 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22120090	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLVAPTAN blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
3.3 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22120090	30 mg 1 times / day multiple, oral dose: 30 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TOLVAPTAN blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22130104/	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:		TOLVAPTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22130104/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:		TOLVAPTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
480 mg single, oral Highest studied dose Dose: 480 mg Route: oral Route: single Dose: 480 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17925589	healthy, 32 years (range: 20-51 years) Health Status: healthy Age Group: 32 years (range: 20-51 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17925589	Other AEs: Thirst, Urinary frequency... Other AEs: Thirst (6 patients) Urinary frequency (6 patients) Dry mouth (2 patients) Headache NOS (2 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17925589
96 mg 1 times / day steady, oral Dose: 96 mg, 1 times / day Route: oral Route: steady Dose: 96 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf	unhealthy, 39 years Health Status: unhealthy Age Group: 39 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf	Disc. AE: Pollakiuria, Polyuria... AEs leading to discontinuation/dose reduction: Pollakiuria (6.6%) Polyuria (6.6%) Nocturia (6.6%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf
300 mg 1 times / day multiple, oral Highest studied dose Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf	healthy, adult Health Status: healthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf
1 mg single, intravenous Dose: 1 mg Route: intravenous Route: single Dose: 1 mg Sources: https://pubmed.ncbi.nlm.nih.gov/22257581	healthy, adult Health Status: healthy Age Group: adult Sources: https://pubmed.ncbi.nlm.nih.gov/22257581	Sources: https://pubmed.ncbi.nlm.nih.gov/22257581
60 mg 1 times / day steady, oral Recommended Dose: 60 mg, 1 times / day Route: oral Route: steady Dose: 60 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf	Other AEs: Liver injury... Other AEs: Liver injury (serious) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf

AEs

AE	Significance	Dose	Population
Dry mouth	2 patients	480 mg single, oral Highest studied dose Dose: 480 mg Route: oral Route: single Dose: 480 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17925589	healthy, 32 years (range: 20-51 years) Health Status: healthy Age Group: 32 years (range: 20-51 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17925589
Headache NOS	2 patients	480 mg single, oral Highest studied dose Dose: 480 mg Route: oral Route: single Dose: 480 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17925589	healthy, 32 years (range: 20-51 years) Health Status: healthy Age Group: 32 years (range: 20-51 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17925589
Thirst	6 patients	480 mg single, oral Highest studied dose Dose: 480 mg Route: oral Route: single Dose: 480 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17925589	healthy, 32 years (range: 20-51 years) Health Status: healthy Age Group: 32 years (range: 20-51 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17925589
Urinary frequency	6 patients	480 mg single, oral Highest studied dose Dose: 480 mg Route: oral Route: single Dose: 480 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17925589	healthy, 32 years (range: 20-51 years) Health Status: healthy Age Group: 32 years (range: 20-51 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17925589
Nocturia	6.6% Disc. AE	96 mg 1 times / day steady, oral Dose: 96 mg, 1 times / day Route: oral Route: steady Dose: 96 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf	unhealthy, 39 years Health Status: unhealthy Age Group: 39 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf
Pollakiuria	6.6% Disc. AE	96 mg 1 times / day steady, oral Dose: 96 mg, 1 times / day Route: oral Route: steady Dose: 96 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf	unhealthy, 39 years Health Status: unhealthy Age Group: 39 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf
Polyuria	6.6% Disc. AE	96 mg 1 times / day steady, oral Dose: 96 mg, 1 times / day Route: oral Route: steady Dose: 96 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf	unhealthy, 39 years Health Status: unhealthy Age Group: 39 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf
Liver injury	serious	60 mg 1 times / day steady, oral Recommended Dose: 60 mg, 1 times / day Route: oral Route: steady Dose: 60 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946			inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 910 NTCP 39 BSEP 550 MATE1 415 MATE2 267 MRP2 499 MRP3 246 MRP4 290 OAT1 725 OAT3 747 OATP1B1 1079 OATP1B3 961 OCT1 620 OCT2 779 P-gp 1741	P-gp 2052

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
OCT1 656	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=5 Page: 6.0	yes [IC50 0.837 uM]
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=6 Page: 6,11	yes [IC50 15.9 uM]	weak (co-administration study) Comment: administration with digoxin increased Digoxin Cmax and AUC by 30% and 20%, respectively Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=6 Page: 6,11
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	yes [IC50 27.2 uM]
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=5 Page: 6.0	yes [IC50 4.14 uM]
NTCP 40	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=16 Page: 16.0	yes [IC50 41.5 uM]
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=5 Page: 6.0	yes [IC50 5.47 uM]
MRP2 625	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=5 Page: 6.0	yes [IC50 50 uM]
MRP3 326	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=5 Page: 6.0	yes [IC50 50 uM]
MRP4 345	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=5 Page: 6.0	yes [IC50 50 uM]
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=5 Page: 6.0	yes [IC50 6.15 uM]
MATE1 416	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=5 Page: 6.0	yes [IC50 7.965 uM]
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=6 Page: 6,11	yes [IC50 8.32 uM]
MATE2 267	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=5 Page: 6.0	yes [IC50 >10 uM]
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=5 Page: 6.0	yes [IC50 >30 uM]
BSEP 554	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=5 Page: 6.0	yes [Ki 34 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	yes
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=96 Page: 96.0	yes		yes (co-administration study) Comment: administration with ketoconazole caused a 3.5-fold and 5-fold increase in tolvaptan Cmax and AUC, respectively; administration with rifmapin reduced Cmax and AUC of tolvaptan to 10 and 20%, respectively; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=96 Page: 96.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022275s000_PharmR_P1.pdf#page=31 Page: 31.0

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY526018	https://www.001chemical.com/chem/150683-30-0
abcr GmbH	AB358162	http://www.abcr.com/shop/en/AB358162
Achemtek	0102-014531	http://www.achemtek.com/150683-30-0
Acorn PharmaTech	ACN-040195	http://www.acornpharmatech.com/
AEchem Scientific Corp., USA	AE1-013459	http://www.aechemsc.com/info_products/AE1-013459.php
AK Scientific, Inc. (AKSCI)	66720	http://www.aksci.com/item_detail.php?cat=66720
Alsachim	2932	http://www.alsachim.com/product-C4002-glo.bal-view.html
Ambinter	Amb17620728	http://www.ambinter.com/reference/17620728
Anward	ANW-59865	http://www.anward.com/pro_result/46316
Ark Pharm	AK-33401	http://www.arkpharminc.com/products/150683-30-0.html
AstaTech, Inc.	40033	http://www.astatechinc.com/CPSResult.php?CRNO=39143
Aurora Fine Chemicals LLC	A13.108.065	http://online.aurorafinechemicals.com/info?ID=A13.108.065
AvaChem Scientific	2634	http://www.avachem.com/productSearch.asp?2634
Axon MedChem	1591	https://www.axonmedchem.com/product/1591
BOC Sciences	1246818-18-7	https://www.bocsci.com/tolvaptan-d7-cas-1246818-18-7-item-484313.html
Boerchem	BC650606	http://www.boerchem.com/?product_38814.html
Chem Scene	CS-0572	http://www.chemscene.com/150683-30-0.html
ChemMol	30115910	http://www.chemmol.com/chemmol/30115910.html
ChemMol	44012557	http://www.chemmol.com/chemmol/44012557.html
ChemMol	49400063	http://www.chemmol.com/chemmol/49400063.html
Chemspace	CSSB00016987605	https://chem-space.com/CSSB00016987605
ChemWise	AR60125	http://www.chemwisellc.com/product/tolvaptan/
ChemWise	AR60127	http://www.chemwisellc.com/product/tolvaptan-2/
Clearsynth	CS-O-02900	https://www.clearsynth.com/en/CSO02900.html
Clearsynth	CS-O-31027	https://www.clearsynth.com/en/CSO31027.html
Clearsynth	CS-T-44605	https://www.clearsynth.com/en/CST44605.html
DC Chemicals	DC9148	http://www.dcchemicals.com/product_show-Tolvaptan.html
eNovation Chemicals	D142062	https://www.enovationchem.com/ProductDetails.asp?ProductID=D142062
Finetech	FT-0675287	http://www.finetechnology-ind.com/prod/detail/pub/331947-66-1.html
Finetech	FT-0675288	http://www.finetechnology-ind.com/prod/detail/pub/331947-44-5.html
Hairui	HR120724	http://www.hairuichem.com/en/product/150683-30-0.html
Hefei Hirisun Pharmatech Co., Ltd	HR130551	http://www.hirisunpharm.com/150683-30-0.html
Hello Bio	HB2651	http://www.hellobio.com/4-methylhistamine-dihydrochloride.html
iChemical	EBD30732	http://www.ichemical.com/products/150683-30-0.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs
Lab Network	LN00196860	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00196860
LGC Standards	MM3561.00	https://www.lgcstandards.com/US/en/p/MM3561.00
Matrix Scientific	94534	https://www.matrixscientific.com/094534.html
MedChem Express	HY-17000	https://www.medchemexpress.com/Tolvaptan.html
Molcore	MC526018	https://www.molcore.com/product/150683-30-0
MolPort	MolPort-008-155-996	https://www.molport.com/shop/molecule-link/MolPort-008-155-996
Oakwood	361970	http://www.oakwoodchemical.com/ProductsList.aspx?CategoryID=-2&txtSearch=150823&ExtHyperLink=1
OChem	24490	http://www.ocheminc.com/index.php?act=psearch&pid=683T300
Shanghai Send Pharmaceutical Technology Co., Ltd	send21416	http://shsendpharm.com/
Sigma-Aldrich	T7455_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/t7455?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sun-shine Chemical	Tolvaptan	http://www.sun-shinechem.com/Details/Tolvaptan/2010/150683-30-0.html
Tocris	5181	https://www.tocris.com/products/tolvaptan_5181
TripleBond	CT0200	http://www.triplebond-canada.com/prod/1632/
Yuhao Chemical	RT9638	http://www.chemyuhao.com/150683-30-0.html

PubMed

Title	Date	PubMed
Polycystic kidney diseases: from molecular discoveries to targeted therapeutic strategies.	2008-02	17975706
Aminocarbonylation route to tolvaptan.	2007-12-01	17933527
Tolvaptan, an oral vasopressin V2 receptor antagonist for heart failure?	2007-12	18037090
Clinical trials update from the European Society of Cardiology Congress in Vienna, 2007: PROSPECT, EVEREST, ARISE, ALOFT, FINESSE, Prague-8, CARESS in MI and ACUITY.	2007-12	17992567
Pharmacokinetics, pharmacodynamics, and safety of tolvaptan, a nonpeptide AVP antagonist, during ascending single-dose studies in healthy subjects.	2007-12	17925589
Diagnosis and management of hyponatremia in cancer patients.	2007-12	17701059
Effects of nonpeptide vasopressin V2 antagonist tolvaptan in rats with heart failure.	2007-11-15	17720144
Current issues for nurse practitioners: Hyponatremia.	2007-11	17970857
Hyponatremia and vasopressin antagonism in congestive heart failure.	2007-11	17847041
Gateways to clinical trials.	2007-10-09	17922073
Water in health and disease: new aspects of disturbances in water metabolism.	2007-10	17954951
V2 receptor antagonism with tolvaptan in heart failure.	2007-10	17922627
[Vasopressin antagonists in treatment of hyponatremia].	2007-08	18018383
Pharmacokinetic and pharmacodynamic interaction between tolvaptan, a non-peptide AVP antagonist, and furosemide or hydrochlorothiazide.	2007-08	17703139
Effects of tolvaptan, an oral vasopressin V2 receptor antagonist, in hyponatremia.	2007-08	17660019
Arginine vasopressin receptor antagonists for heart failure: a winter climbing to the Everest's tip?	2007-06-05	17543635
Multicenter, randomized, double-blind, placebo-controlled study on the effect of oral tolvaptan on left ventricular dilation and function in patients with heart failure and systolic dysfunction.	2007-06-05	17543634
[Recent progress in vasopressin research on cardiovascular diseases].	2007-06	17657988
Vaptans: a promising therapy in the management of advanced cirrhosis.	2007-06	17445935
[Vasopressin V2-receptor antagonist, tolvaptan, for treatment of heart failure].	2007-05-28	17571379
What new drugs can nephrologists look forward to in the next year or two?	2007-05	17457357
Hyponatremia: current treatment strategies and the role of vasopressin antagonists.	2007-05	17405824
Clinical trials update from the American College of Cardiology 2007: ALPHA, EVEREST, FUSION II, VALIDD, PARR-2, REMODEL, SPICE, COURAGE, COACH, REMADHE, pro-BNP for the evaluation of dyspnoea and THIS-diet.	2007-04-19	17481946
Climbing the mountain of acute decompensated heart failure: the EVEREST Trials.	2007-03-28	17384439
Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials.	2007-03-28	17384438
Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial.	2007-03-28	17384437
Gateways to clinical trials.	2007-03-09	17344945
Tolvaptan for hyponatremia.	2007-03-01	17338053
Tolvaptan for hyponatremia.	2007-03-01	17338052
Tolvaptan for hyponatremia.	2007-03-01	17338051
Tolvaptan for hyponatremia.	2007-03-01	17329708
Gateways to clinical trials.	2007-03	17440629
New agents for managing hyponatremia in hospitalized patients.	2007-02-01	17244874
Recognition and treatment of hyponatremia in acutely ill hospitalized patients.	2007-02	17472815
Evaluation and management of hyponatremia: an emerging role for vasopressin receptor antagonists.	2007-02	17251996
Nephrogenic syndrome of inappropriate antidiuresis in adults: high phenotypic variability in men and women from a large pedigree.	2007-02	17229917
[Arginine vasopressin antagonism--new treatment option in chronic heart failure].	2007-01-18	17237865
Role of vasopressin in rat distal colon function.	2007-01-15	17082233
Clinical trials update from the American Heart Association 2006: OAT, SALT 1 and 2, MAGIC, ABCD, PABA-CHF, IMPROVE-CHF, and percutaneous mitral annuloplasty.	2007-01	17188569
Improvement in hyponatremia during hospitalization for worsening heart failure is associated with improved outcomes: insights from the Acute and Chronic Therapeutic Impact of a Vasopressin Antagonist in Chronic Heart Failure (ACTIV in CHF) trial.	2007	17573581
Tolvaptan, an orally active vasopressin V(2)-receptor antagonist - pharmacology and clinical trials.	2007	17445084
Aquaretic agents: what's beyond the treatment of hyponatremia?	2007	17430186
Therapeutic potential of vasopressin receptor antagonists.	2007	17428103
Cerebral correlates of hyponatremia.	2007	17356196
Comparison of 60-day mortality in hospitalized heart failure patients with versus without hypothermia.	2006-12-01	17126655
Vasopressin antagonists--progress and promise.	2006-11-16	17105758
Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia.	2006-11-16	17105757
Gateways to clinical trials.	2006-09	17003851
AVP receptor antagonists as aquaretics: review and assessment of clinical data.	2006-09	16970150
Vasopressin antagonists as aquaretic agents for the treatment of hyponatremia.	2006-07	16843091

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.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:58:01 GMT 2025` Edited by `admin` on `Mon Mar 31 17:58:01 GMT 2025`
Record UNII	21G72T1950
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

JINARC

Preferred Name

English

Tolvaptan

Official Name

English

TOLVAPTAN [ORANGE BOOK]

Common Name

English

OPC-41061

Code

English

N-[4-[(7-Chloro-2,3,4,5-tetrahydro-5-hydroxy-1H-1-benzazepin-1-yl)carbonyl]-3-methylphenyl]-2-methylbenzamide

Systematic Name

English

TOLVAPTAN [MART.]

Common Name

English

SAMSCA

Brand Name

English

JYNARQUE

Brand Name

English

tolvaptan [INN]

Common Name

English

(±)-4'-((7-CHLORO-2,3,4,5-TETRAHYDRO-5-HYDROXY-1H-1-BENZAZEPIN-1-YL) CARBONYL)-O-TOLU-M-TOLUIDIDE

Common Name

English

TOLVAPTAN [EMA EPAR]

Common Name

English

Benzamide, N-[4-[(7-chloro-2,3,4,5-tetrahydro-5-hydroxy-1H-1-benzazepin-1-yl)carbonyl]-3-methylphenyl]-2-methyl-

Systematic Name

English

TOLVAPTAN [MI]

Common Name

English

TOLVAPTAN [VANDF]

Common Name

English

TOLVAPTAN [JAN]

Common Name

English

Tolvaptan [WHO-DD]

Common Name

English

TOLVAPTAN [USAN]

Common Name

English

Classification Tree Code System Code

LIVERTOX

NBK548503