Serelaxin

Revision as of 14:23, 23 July 2014 by GeraldChi (talk | contribs)
Jump to navigation Jump to search
Serelaxin
Clinical data
Pregnancy
category
  • N/A
Routes of
administration
Intravenous
ATC code
Legal status
Legal status
  • Investigational
Identifiers
CAS Number
ChemSpider
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC256H408N74O74S8
Molar mass5963 g/mol

WikiDoc Resources for Serelaxin

Articles

Most recent articles on Serelaxin

Most cited articles on Serelaxin

Review articles on Serelaxin

Articles on Serelaxin in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Serelaxin

Images of Serelaxin

Photos of Serelaxin

Podcasts & MP3s on Serelaxin

Videos on Serelaxin

Evidence Based Medicine

Cochrane Collaboration on Serelaxin

Bandolier on Serelaxin

TRIP on Serelaxin

Clinical Trials

Ongoing Trials on Serelaxin at Clinical Trials.gov

Trial results on Serelaxin

Clinical Trials on Serelaxin at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Serelaxin

NICE Guidance on Serelaxin

NHS PRODIGY Guidance

FDA on Serelaxin

CDC on Serelaxin

Books

Books on Serelaxin

News

Serelaxin in the news

Be alerted to news on Serelaxin

News trends on Serelaxin

Commentary

Blogs on Serelaxin

Definitions

Definitions of Serelaxin

Patient Resources / Community

Patient resources on Serelaxin

Discussion groups on Serelaxin

Patient Handouts on Serelaxin

Directions to Hospitals Treating Serelaxin

Risk calculators and risk factors for Serelaxin

Healthcare Provider Resources

Symptoms of Serelaxin

Causes & Risk Factors for Serelaxin

Diagnostic studies for Serelaxin

Treatment of Serelaxin

Continuing Medical Education (CME)

CME Programs on Serelaxin

International

Serelaxin en Espanol

Serelaxin en Francais

Business

Serelaxin in the Marketplace

Patents on Serelaxin

Experimental / Informatics

List of terms related to Serelaxin

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2]

Overview

Serelaxin (RLX030) is an investigational drug for the treatment of acute heart failure (AHF), targeting the relaxin receptor. Serelaxin is a recombinant form of human relaxin-2, a hormone that (among other functions) is produced during pregnancy and mediates the haemodynamic changes that occur during this time, such as increased blood output of the heart and blood flow in the kidney. Human-relaxin-2 mediates vasodilation (widening of blood vessels) by increasing the production of nitric oxide (NO), a potent vasodilator. Activation of the relaxin receptor RXFP1 activates several enzymes in a phosphorylation cascade that eventually results in the activation of NO synthase in endothelial cells and the subsequent production of NO. Relaxin can also bind to a secondary receptor, endothelial B receptor, which is upregulated as a result of the previous pathway. Relaxin binding to endothelial B receptor on endothelial cells also induces vasodilation.

Relaxin causes vasodilation by an indirect mechanism, where it inhibits the potent vasoconstrictors angiotensin II and endothelin. In addition to vasodilation, the effects of relaxin are also seen in the kidneys, by significantly increasing creatinine clearance, which is a measure of kidney function, as well as increased renal blood flow. Relaxin also functions as a cardiac stimulant. Studies have demonstrated that relaxin increases calcium sensitivity of cardiac myofilaments as well as increasing phosphorylation of the myofilaments by protein kinase C (PKC). These modifications both function to increase the force generated by the myofilaments without increasing the energy consumption of the cardiac myocytes. Thus relaxin and serelaxin can increase stroke volume, the amount of blood pumped per heart beat, without increasing the energy demand on the already strained heart of acute heart failure patients.

Acute heart failure

Serelaxin is currently undergoing clinical trials in patients with acute heart failure, and is being developed by Novartis. Serelaxin has completed several clinical trials as a therapy for AHF. Phase I trials examined safety and tolerability, while phase II trials evaluated its haemodynamic effects and symptom relief. The Pre-RELAX-AHF phase II trial administered a dose of 30 µg/kg/day and showed a decrease in blood pressure, improved dyspnoea, and increased renal blood flow. In phase III the RELAX-AHF trial gave a 48hr intravenous infusion of the same dose. It significantly improved patients' dyspnoea, resulted in a 30% reduction in worsening of heart failure symptoms, a decreased hospital stay and a reduction in signs and symptoms of congestion. The FDA has granted serelaxin "breakthrough therapy" designation, meant to expedite the development and review of drugs for life threatening conditions and is set to be reviewed in February 2014.

References