Riociguat for the treatment of pulmonary hypertension

Expert Opin Investig Drugs. 2011 Apr;20(4):567-76. doi: 10.1517/13543784.2011.565048. Epub 2011 Mar 11.

Abstract

Introduction: Pulmonary hypertension (PH) is a severe condition with a poor prognosis despite recent treatment advances. Therapies with new mechanisms of action are needed.

Areas covered: This review will help readers understand the mechanism of action of the soluble guanylate cyclase (sGC) stimulator riociguat (BAY 63-2521) and will provide a comprehensive summary regarding efficacy and safety of this drug in the management of PH. The most relevant publications up to December 2010 were used as sources for this review.

Expert opinion: Cyclic guanosine monophosphate (cGMP) is an important mediator of the preferential perfusion of well-ventilated regions throughout the lung. Drugs that increase cGMP levels could promote pulmonary vasorelaxation while maintaining optimal gas exchange. cGMP is generated by sGC, which can be stimulated by nitric oxide (NO). Riociguat stimulates sGC independently of NO and increases the sensitivity of sGC to NO, resulting in increased cGMP levels. Results to date suggest rapid, potent and prolonged efficacy and good tolerability in different types of PH. Phase III clinical trials are evaluating the long-term safety and clinical effectiveness of riociguat in pulmonary arterial hypertension (PAH) and chronic thromboembolic PH. Riociguat has the potential to become an important drug for the treatment of patients with PH.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antihypertensive Agents / pharmacology*
  • Antihypertensive Agents / therapeutic use*
  • Clinical Trials as Topic
  • Drug Evaluation, Preclinical
  • Guanylate Cyclase
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Models, Cardiovascular
  • Pyrazoles / pharmacology*
  • Pyrazoles / therapeutic use*
  • Pyrimidines / pharmacology*
  • Pyrimidines / therapeutic use*
  • Receptors, Cytoplasmic and Nuclear / agonists
  • Soluble Guanylyl Cyclase

Substances

  • Antihypertensive Agents
  • Pyrazoles
  • Pyrimidines
  • Receptors, Cytoplasmic and Nuclear
  • Guanylate Cyclase
  • Soluble Guanylyl Cyclase
  • riociguat