Senazodan hydrochloride

Senazodan (MCI 154) (hydrochloride), as a Ca2+ sensitiser, shows inhibition effect on PDE III[1][2].

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Metabolic Enzyme/Protease >> Phosphodiesterase (PDE)

PDE III[1]

Senazodan (hydrochloride) seems to affect directly the actin-myosin crossbridge kinetics, and increases myosin ATPase activity[1]. Senazodan (hydrochloride) produces a concentration-dependent increase in tension development. Senazodan (hydrochloride) enhances Ca2+ binding to myofilaments and to purified cardiac troponin C. Senazodan (hydrochloride) also enhances contractility in guinea-pig papillary muscles by inhibiting PDE III[2].Senazodan (0.1 nM~0.1 mM) (hydrochloride) shows that the contractile response of superior mesenteric arterie (SMA) to norepinephrine (NE) after hemorrhagic shock is significantly decreased as compared with the normal control group. Senazodan (0.01 mM) (hydrochloride) pretreatment prevents the effects of Ang II, and the concentration-response curve of Ca2+ is shifted to the right as compared with Ang II-alone group[3].

Senazodan (0.1~2.0 mg/kg; left femoral vein catheterization infusion) (hydrochloride) decreases the pressor effect of norepinephrine (NE)[3]. Senazodan (0.1 mg/kg; i.v.) (hydrochloride) makes LVSP, IP, MC, and Lo all increased significantly, while heart rate is not obviously changed and left ventricular end-diastolic pressure (LVEDP) is reduced remarkably[4]. Animal Model: Wistar rats (200~250 g)[3] Dosage: 0.1~2.0 mg/kg Administration: Left femoral vein catheterization infusion Result: Decreased the pressor effect of norepinephrine (NE). Animal Model: Rabbits[4] Dosage: 0.1 mg/kg Administration: I.v. Result: LVSP, IP, MC, and Lo all were increased significantly while heart rate was not obviously changed and left ventricular end-diastolic pressure (LVEDP) was reduced remarkably.

[1]. Lehtonen LA, et al. Pharmacokinetics and pharmacodynamics of intravenous inotropic agents. Clin Pharmacokinet. 2004;43(3):187-203.

[2]. Erhardt L. An emerging role for calcium sensitisation in the treatment of heart failure. Expert Opin Investig Drugs. 2005 Jun;14(6):659-70.

[3]. Yang G, et al. Effects of MCI-154 on vascular reactivity and its mechanisms after hemorrhagic shock in rats. J Cardiovasc Pharmacol. 2006;47(6):751-757.

[4]. Ming MJ, et al. Effects of MCI-154, a calcium sensitizer, on cardiac dysfunction in endotoxic shock in rabbits. Shock. 2000;13(6):459-463.