OR-1896

OR-1896 is an active long-lived metabolite of Levosimendan. OR-1896 is a highly selective phosphodiesterase (PDE) III isoform inhibitor and a powerful vasodilator. OR-1896 can open ATP-sensitive K+ channels and has Ca2+-sensitizing effect. OR-1896 mitigates cardiomyocyte apoptosis, cardiac remodeling and myocardial inflammation[1].

Research Areas >> Cardiovascular Disease

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

Signaling Pathways >> Membrane Transporter/Ion Channel >> Potassium Channel

PDE3/PDE Ⅲ

K+ Channel

Drug Metabolite

There are many evidences has accumulated and revealed a variety of beneficial pleiotropic effects OR-1896. OR-1896 evokes prominent vasodilatory responses, activation of ATP-sensitive sarcolemmal K+ channels of smooth muscle cells appears as a powerful vasodilator mechanism. Additionally, activation of ATP-sensitive K+ channels in the mitochondria potentially extends the range of cellular actions towards the modulation of mitochondrial ATP production and implicates a pharmacological mechanism for cardioprotection[1].

During the metabolism of Levosimendan approximately 5% of the drug is converted to the metabolite OR-1855 in the large intestine, and then acetylated in the liver to form the active metabolite OR-1896. Binding to plasma proteins is 98% for Levosimendan but only 40% for OR-1896. Unlike Levosimendan, which has an elimination half-life of 1-1.5 h, the half-life of OR-1896 is about 75 to 80 h allowing cardiovascular effects to persist up to 7 to 9 days after discontinuation of a 24-hour infusion of levosimendan. The pharmacokinetic of the parent drug is unaltered in subjects with severe renal impairment or with moderate hepatic impairment, whereas the elimination of its metabolites (OR-1896) can be prolonged[1].

[1]. Papp, Z, et al., Levosimendan: molecular mechanisms and clinical implications: consensus of experts on the mechanisms of action of levosimendan. Int J Cardiol. 2012 Aug 23;159(2):82-7.