Ivabradine hydrochloride

Description

In an effort to develop angina agents without the unwanted negative inotropic and hypotensive effects associated with b-adrenergic blockers and calcium channel blockers, a new class of heart-rate reducing compounds that act specifically on the sinoatrial (SA) node has been explored. These bradycardic agents interact directly with the pacemaking cell of the SA node and the hyperpolarization- activated If , the primary pacemaking current. Ivabradine has evolved as a specific inhibitor of If current through its contact with f-channels on the intracellular side of the plasma membrane. As a consequence, ivabradine reduces the speed of diastolic depolarization and decreases heart rate. It has been approved for the treatment of chronic stable angina and provides a viable alternative to patients with a contraindication or intolerance of b-blockers. Evaluation is also underway for the potential treatment of ischemic heart disease. Using a patch-clamp technique on rabbit sinoatrial node cells, inhibition of If current ranged from 6% (0.03 mM) – 80% (10 mM). .

Chemical properties

White to Off-White Solid

Originator

Servier (France)

The Uses of Ivabradine hydrochloride

Ivabradine hydrochloride has been used as a potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel (HCN)2 blocker in embryoid body (EB) and rat engineered heart tissue (EHT).

The Uses of Ivabradine hydrochloride

Selective bradycardic agent with direct effect on the pacemaker If current of the sinoatrial node. Antianginal

The Uses of Ivabradine hydrochloride

Ivabradine HCl, a new If inhibitor with IC 50 of 2.9 μM which acts specifically on the pacemaker activity of the sinoatrial node, is a pure heart rate lowering agent

The Uses of Ivabradine hydrochloride

angina therapeutic

Definition

ChEBI: A hydrochloride obtained by combining ivabradine with one molar equivalent of hydrochloric acid. Used to treat patients with angina who have intolerance to beta blockers and/or heart failure.

Mechanism of action

Ivabradine Hydrochloride selectively binds to the intracellular portion of the HCN channel pore and blocks HCN channels in the pacemaker cells within the sinoatrial (SA) node. This inhibits the If (funny) pacemaker ion current, prevents the inward flow and intracellular accumulation of positively charged ions, reduces pacemaker activity and slows diastolic depolarization. This decreases heart rate, reduces myocardial oxygen demand and allows more time for blood to flow to the myocardium without affecting cardiac contractility.

brand name

Procoralan

Biochem/physiol Actions

Ivabradine is used to treat chronic heart failure.

Clinical Use

Symptomatic treatment of chronic stable angina pectoris in patients with sinus rhythm Treatment of mild to severe chronic heart failure

storage

Store at -20°C