Istaroxime hydrochloride

General description:

Product group: Chemicals

Category: Other

CAS No: 374559-48-5

Properties:

Purity:> 98%

Molecular Formula: C21H33ClN2O3

Molecular weight: 396.95

UNSPSC: 12352200

Scientific information:

Istaroxime Hcl (PST-2744 Hcl) is a positive inotropic agent that mediates its action by inhibiting sodium / potassium adenosine triphosphatase (Na + / K + ATPase). IC50 value: 0.43 +/- 0.15 uM (dog kidney Na + / K + -ATPase activity) Target: Na + / K + ATPase Istaroxime is an investigational drug originally patented and developed by the Italian pharmaceutical company Sigma-Tau. Istaroxime is now in development for the treatment of acute decompensated heart failure by CVie Therapeutics. in vitro: PST2744 inhibited dog kidney Na + / K + -ATPase activity with an IC50 value of 0.43 +/- 0.15 uM [1]. The transient inrush current (I (TI)) induced by a Ca (2+) transient in the presence of complete Na (+) / K (+) pump block was inhibited (-43%) by PST2744 but not by digoxin. in vivo: intravenous infusion of 0.2 mg / kg / min of PST2744 in anesthetized guinea pigs exerted an immediate and long-lasting inotropic effect (SD (80) of 1.89 +/- 0.37 mg / kg) without causing lethal arrhythmias up to a cumulative dose of 18 mg / kg.

Intravenous infusion of istaroxime (0.11 mg / kg per min) significantly increased contraction and relaxation rates (fractional shortening, +18 +/- 3.7%, aortic flow rate, +19 +/- 2.9 %, maximum myocardial systolic velocity, +36 +/- 7%, circumferential fiber shortening, +24 +/- 4.1%, maximum atrial flow velocity, +69 +/- 8.6%, relaxation time isovolumic, +19 +/- 6.9% and myocardial early diastolic maximum velocity, +42 +/- 12%). In 5 animals, the effects of PST-2744 were compared with dobutamine. Heart rate, PR intervals, and QT intervals were unchanged after PST-2744 administration. PST-2744 increased contractility (+ dP / dt) by 56% from 1881 +/- 282 mm Hg / s to 2939 +/- 734 mm Hg / s (P <0.01) [4]. Clinical trial: HORIZON-HF: phase II trial to evaluate the hemodynamic effects of istaroxime in patients with worsening HF and decreased LV systolic function.

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