By overcoming the odds of mortality in the dreaded acute heart failure by as far as 37 percent, Serelaxin has been rightly named as a “breakthrough therapy” by the US Food and Drug administration (FDA). Originally developed by one of the leading pharmaceuticals company, Novartis, Serelaxin is a recombinant analogue of the human pregnancy hormone Relaxin known for its regulatory hemodynamic functions to bear the load of the foetus.
Human relaxin, a peptide hormone secreted by corpus luteum is known to target the relaxin receptors and mediate various vascular changes during pregnancy to accommodate the foetus. The blood levels of relaxin undergo a significant surge during pregnancy and birth to increase the cardiac output as well as the renal blood circulation both phenomena being essential for adjusting blood circulation to the foetus.
Mechanism of Action of Relaxin
Relaxin acts via several mechanisms to widen blood vessels and improve the cardiac output as well as renal blood flow:-
- It activates relaxin receptor RFXP1 which lead to the activation of various enzyme components of a phosphorylation cascade. This cascade finally activates the enzyme nitric oxide synthase in the endothelial cells which ultimately produce nitric oxide, an expert vasodilator.
- It also binds to either of the receptors LGR7 or LGR8 which activates a G-protein coupled receptor pathway in endothelium of blood vessels. This results in secondary endothelial B cell receptor activation and upregulation of vascular endothelial growth factor(VEGF) which contribute to vasodilation.
- Relaxin induces vasodilation in an indirect pathway as well. It deactivates angiotensin-II and endothelin both of which have dominant vasoconstrictor properties.
- It dilates the efferent and the afferent arterioles of the kidney to improve blood flow in kidneys. It has been found to increase creatinine clearance which is an undisputed indicator of improved renal blood flow as well as kidney functions.
- It stimulates the myocardial fibres by not only increasing their response to calcium ions but also by increasing phosphorylation of the filaments of myocardium by the enzyme protein kinase C. These changes increase the intensity of force produced by myocardium without any rise in the energy demand of the cardiac myofilaments.
All the above changes lead to a surge in the volume of blood pumped by the heart per beat without increasing the load on the already weakened heart in individuals with acute heart failure.
Legal status of Serelaxin
Serelaxin has been assigned the status of a breakthrough “investigational” intravenous drug, since it is under clinical trials in patients with acute heart failure. It has been undergoing trials of safety, tolerability and its effects on hemodynamic states and symptom relief. Some trials have advocated its effects by showing a decrease in blood pressure, improving dyspnoea (a classic heart failure symptom) as well as enhancing renal blood flow while the others showed a significant decrease in hospital stay and a drop in symptoms of congestion which are very specific to acute heart failure patients.
Joint efforts of pharmacological experts, research doctors and healthcare industries are still in process to approve the status of serelaxin as drug therapy for heart diseases.