Ivabradine
A special issue of Molecules (ISSN 1420-3049).
Deadline for manuscript submissions: closed (30 May 2012) | Viewed by 34082
Special Issue Editor
Interests: atherosclerosis; statins; ivabradine; ischemic cardiac disease; antioxidants; endothelial dyfunction and metabolities; carotenoids
Special Issues, Collections and Topics in MDPI journals
Special Issue Information
Dear Colleagues,
Ivabradine (IVA) is a novel specific heart rate (HR) lowering agent that acts in sinoatrial node (SAN) cells by selectively inhibiting the pacemaker If current in a dose–dependent manner by slowing the diastolic depolarization slope of SAN cells, and reducing HR at rest and during exercise with minimal effect on myocardial contractility, blood pressure, and intracardiac conduction.
The cardiac pacemaker cells, the first cells which generate the electrical impulse and form SAN, have the specific feature of spontaneous electrical activity generating repetitive action potentials at a specific controlled rate.
Among the different currents at the basis of the mechanisms contributing to electrical stimulus, the If current has a major role in providing pacemaking competence. Originally this current was described in the SAN the funny current and its properties in cardiac pacemaker cells have been the object of intense investigations. Funny channels underlie the cardiac pacemaker If current, originally described as an inward current activated on hyperpolarization to the diastolic range of voltages in SAN myocytes.
SAN cells can depolarize spontaneously. This depolarization is due to the movement of ions (sodium and potassium) across specialized membrane channels, which directly modulates the rate of spontaneous diastolic depolarization. The If current is important in the generation of pacemaking not only for diastolic–depolarization but also for its involvement in neurotransmitter–induced control of cardiac rate. It was shown since its first description that If mediates the acceleratory effect of adrenaline on pacemaker rate and a later study showed its strongly modulation by acetylcholine but with opposite action regard that of catecholamines.
The molecular basis of the If current and its related equivalent in non–cardiac cells If have been characterized by cloning a family of ionic channels, known as hyperpolarization–activated cyclic nucleotide–gated channels (HCN). Four isoforms of HCN have been identified, HCN1–4 which show typical characteristics of pacemaker currents, activation on hyperpolarization, current carried by sodium and potassium ions, modulation by cyclic adenosine monophosphate and sensitivity to caesium.
Detailed patch–clamp studies in rabbit SAN cells have shown that the drug blocks If channels and that it interacts with the channels from the intracellular side.33 More recently, also in SAN cells, IVA has been shown to be an open channel blocker, indicating that it cannot reach its binding site when the channels are closed, and its blocking effect is current–dependent and is attenuated during very long hyperpolarized pulses (more than 20 seconds of hyperpolarization).
The possibility to modulate the If current offers new therapeutic options for the control of cardiac chronotropism. The development of molecules that interact specifically with funny channels is the basis of new pharmacological approaches to the management of HR. The aim of this special issue is to examinate the most important aspects will regard the synthesis, biological activities and pharmacokinetic-pharmacodynamic aspects.
Dr. Graziano Riccioni
Guest Editor
Keywords
- ivabradine
- medicinal chemistry
- If current
- sino-atrial node
- synthesis
- HCN channels
- heart rate
- funny current
Benefits of Publishing in a Special Issue
- Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
- Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
- Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
- External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
- e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.
Further information on MDPI's Special Issue polices can be found here.
Related Special Issue
- Ivabradine in Pharmaceuticals (1 article)
