Elsevier

International Journal of Cardiology

Volume 203, 15 January 2016, Pages 543-548
International Journal of Cardiology

Review
Calcium sensitizers: What have we learned over the last 25 years?

https://doi.org/10.1016/j.ijcard.2015.10.240Get rights and content
Under a Creative Commons license
open access

Highlights

  • Review of cardioactive drugs with calcium sensitization as mechanism of action

  • Analysis of the pharmacology and clinical effects of calcium sensitizers

  • Comparison of ‘calcium sensitizers’ with ‘calcium mobilizers’

  • Role of the pleiotropic effects of some calcium sensitizers such as levosimendan

Abstract

The use of inotropes for correcting hemodynamic dysfunction in patients with congestive heart failure has been described over many decades. Drugs such as cardiac glycosides, cathecolamines, phosphodiestherase inhibitors, and calcium sensitizers have been in turn proposed. However, the number of new chemical entities in this therapeutic field has been surprisingly low, and the current selection of drugs is limited. One of the paradigm shifts in the discovery for new inotropes was to focus on ‘calcium sensitizers’ instead of ‘calcium mobilizers’. This was designed to lead to the development of safer inotropes, devoid of the complications that arise due to increased intracellular calcium levels. However, only three such calcium sensitizers have been fully developed over the latest 30 years. Moreover, two of these, levosimendan and pimobendan, have multiple molecular targets and other pharmacologic effects in addition to inotropy, such as peripheral vasodilation. More recently, omecamtiv mecarbil was described, which is believed to have a pure inotropy action that is devoid of pleiotropic effects. When the clinical data of these three calcium sensitizers are compared, it appears that the less pure inotropes have the cutting edge over the purer inotrope, due to additional effects during the treatment of a complex syndrome such as acute congested heart failure. This review aims to answer the question whether calcium sensitization per se is a sufficient strategy for bringing required clinical benefits to patients with heart failure. This review is dedicated to the memory of Heimo Haikala, a true and passionate innovator in this challenging field.

Keywords

Inotropes
Inodilators
Troponin C
Myosin
Cardiovascular pharmacology
Heart failure

Cited by (0)

In memory of Heimo Haikala, PhD.