Conivaptan HCl (YM 087) 168626-94-6_Vasopressin Receptor_GPCR & G Protein_Signaling Pathways_Products

Conivaptan HCl (formerly known as YM-087; YM087; YM 087, trade name Vaprisol), the hydrochloride salt of It inhibits the rat liver V1A receptor and the rat kidney V2 receptor with Ki values of 0.48 and 3.04 nM, respectively. Conivaptan was licensed in 2004 for the treatment of hyponatremia (low blood sodium levels) brought on by syndrome of inappropriate antidiuretic hormone (SIADH), including hypervolemic and euvolemic cases.There is also some indication that the drug may be useful in heart failure cases. Conivaptan suppresses the activity of the vasopressin receptor's two (V1a and V2) subtypes.

Physicochemical Properties

Molecular Formula

C32H26N4O2.HCL

Molecular Weight

535.04

Exact Mass

534.182

Elemental Analysis

C, 71.84; H, 5.09; Cl, 6.63; N, 10.47; O, 5.98

CAS #

168626-94-6

Related CAS #

168626-94-6(HCl)

PubChem CID

216322

Appearance

White to off-white solid powder

Boiling Point

751.2ºC at 760 mmHg

Melting Point

>250°

Flash Point

408.1ºC

Vapour Pressure

1.89E-22mmHg at 25°C

LogP

7.447

Hydrogen Bond Donor Count

Hydrogen Bond Acceptor Count

Rotatable Bond Count

Heavy Atom Count

Complexity

820

Defined Atom Stereocenter Count

SMILES

Cl[H].O=C(C1C([H])=C([H])C(=C([H])C=1[H])N([H])C(C1=C([H])C([H])=C([H])C([H])=C1C1C([H])=C([H])C([H])=C([H])C=1[H])=O)N1C2=C([H])C([H])=C([H])C([H])=C2C2=C(C([H])([H])C1([H])[H])N([H])C(C([H])([H])[H])=N2

InChi Key

BTYHAFSDANBVMJ-UHFFFAOYSA-N

InChi Code

InChI=1S/C32H26N4O2.ClH/c1-21-33-28-19-20-36(29-14-8-7-13-27(29)30(28)34-21)32(38)23-15-17-24(18-16-23)35-31(37)26-12-6-5-11-25(26)22-9-3-2-4-10-22;/h2-18H,19-20H2,1H3,(H,33,34)(H,35,37);1H

Chemical Name

N-[4-(2-methyl-4,5-dihydro-3H-imidazo[4,5-d][1]benzazepine-6-carbonyl)phenyl]-2-phenylbenzamide;hydrochloride

Synonyms

Conivaptan hydrochloride; YM-087 HCl; Conivaptan; Conivaptan; YM 087; YM087; Vaprisol

HS Tariff Code

2934.99.9001

Storage

Powder-20°C 3 years

4°C 2 years

In solvent -80°C 6 months

-20°C 1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

Shipping Condition

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets

Vasopressin receptor 1; Vasopressin receptor 2

ln Vitro

In vitro activity: Conivaptan (hydrochloride) is a non-peptide vasopressin receptor antagonist; its Ki values for the rat kidney V2 receptor and liver V1A receptor are 3.04 nM and 0.48 nM, respectively.

ln Vivo

Conivaptan (0.03, 0.1, and 0.3 mg/kg, intravenously) increases urine volume and decreases urine osmolality in rats with myocardial infarction and rats undergoing sham surgery in a dose-dependent manner. Conivaptan (0.3 mg/kg intraperitoneally) dramatically lowers lung/body weight, right atrial pressure, left ventricular end-diastolic pressure, and right ventricular systolic pressure in myocardial infarction rats. Myocardial infarction rats' dP/dt(max)/left ventricular pressure are significantly increased by conivaptan (0.3 mg/kg i.v.)[1]. At the conclusion of the study, cirrhotic rats given the V(1a)/V(2)-AVP receptor antagonist did not exhibit hyponatremia or hypoosmolality. Conivaptan causes an acute increase in urine volume (UV) and a decrease in osmolality (UOsm). Conivaptan also returns U(Na)V to normal while leaving arterial pressure and creatinine clearance unchanged[2]. Conivaptan (0.01 to 0.1 mg/kg, i.v.) inhibits the pressor effect of exogenous vasopressin in a dose-dependent manner (0.003 to 0.1 mg/kg i.v.), and at the highest dose (0.1 mg/kg i.v.), almost entirely blocks vasoconstriction brought on by exogenous vasopressin in dogs without increasing the amount of electrolyte excretion in the urine. In dogs with congestive heart failure, conivaptan (0.1 mg/kg, i.v.) decreases preload and afterload as shown by significant reductions in left ventricular end-diastolic pressure and total peripheral vascular resistance[3]. It also improves cardiac function as demonstrated by significant increases in left ventricular dP/dtmax, cardiac output, and stroke volume.

Animal Protocol

Forty-nine myocardial infarction rats were still alive four weeks after the surgery. Thirty are chosen at random, impartially, and placed into five groups based on similarity in body weight and infarct size distribution. Each group is then administered conivaptan (0.03, 0.1, and 0.3 mg/kg) or SR121463A (0.3 mg/kg) intravenously. Additionally, four groups of sham rats are created and intravenous conivaptan (0.03, 0.1, and 0.3 mg/kg) or vehicle is administered. After that, rats are put in separate metabolic cages, and urine is collected for three hours. Using an osmometer and the freezing point depression method, urine osmolality is determined.

References

[1]. Intravenous administration of conivaptan hydrochloride improves cardiac hemodynamics in rats with myocardial infarction-induced congestive heart failure. Eur J Pharmacol. 2005 Jan 10;507(1-3):145-51. Epub 2005 Jan 1.

[2]. Effect of the V1a/V2-AVP receptor antagonist, Conivaptan, on renal water metabolism and systemic hemodynamics in rats with cirrhosis and ascites. J Hepatol. 2003 Jun;38(6):755-61.

[3]. Cardiovascular and renal effects of conivaptan hydrochloride (YM087), a vasopressin V1A and V2 receptor antagonist, in dogs with pacing-induced congestive heart failure. Eur J Pharmacol. 1999 Jul 9;376(3):239-46.

Additional Infomation

Conivaptan hydrochloride is the hydrochloride salt of conivaptan. It is an antagonist for two of the three types of arginine vasopressin (AVP) receptors, V1a and V2, and is used for the treatment of hyponatraemia (low blood sodium levels) caused by syndrome of inappropriate antidiuretic hormone (SIADH). It has a role as a vasopressin receptor antagonist and an aquaretic. It contains a conivaptan.
See also: Conivaptan (has active moiety).

Solubility Data

Solubility (In Vitro)

DMSO: ~107 mg/mL (~200 mM)

Water: <1 mg/mL

Ethanol: ~7 mg/mL (~13.1 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.67 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 2.5 mg/mL (4.67 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

Solubility in Formulation 3: ≥ 2.5 mg/mL (4.67 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.8690 mL	9.3451 mL	18.6902 mL
	5 mM	0.3738 mL	1.8690 mL	3.7380 mL
	10 mM	0.1869 mL	0.9345 mL	1.8690 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

PeptideDB

Conivaptan HCl (YM 087) 168626-94-6

CAS No.: 168626-94-6

Physicochemical Properties

Biological Activity

Solubility Data