Document Detail

Soluble guanylate cyclase stimulation: an emerging option in pulmonary hypertension therapy.
MedLine Citation:
PMID:  20956121     Owner:  NLM     Status:  MEDLINE    
The prognosis for patients with pulmonary hypertension remains poor despite recent treatment advances, and there is a need for therapies with new modes of action. Nitric oxide (NO) is an endogenous vasodilator, the levels of which are regulated throughout the lung to ensure preferential perfusion of well-ventilated regions. Drugs that act in synergy with endogenous NO would therefore promote pulmonary vasodilation while maintaining optimal gas exchange. Riociguat is an oral stimulator of the NO receptor soluble guanylate cyclase. It synergises with NO and has demonstrated vasodilatory and antiremodelling properties in preclinical studies. Riociguat has been shown to have a favourable safety profile in healthy volunteers and in patients with pulmonary hypertension. Pharmacokinetic analyses have revealed substantial interindividual variation, suggesting that individual dose titration will be required. In a proof-of-concept study of patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension, riociguat improved cardiopulmonary haemodynamics from baseline. It also caused systemic vasodilation, which was well tolerated but should be monitored in future studies. Dose titration of riociguat should promote pulmonary vasodilation while maintaining control of systemic effects, and has been investigated in a phase-II study of patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. Preliminary results indicate that phase-III trials are warranted.
H A Ghofrani; F Grimminger
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  European respiratory review : an official journal of the European Respiratory Society     Volume:  18     ISSN:  1600-0617     ISO Abbreviation:  Eur Respir Rev     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2010-10-19     Completed Date:  2011-02-07     Revised Date:  2012-01-10    
Medline Journal Info:
Nlm Unique ID:  9111391     Medline TA:  Eur Respir Rev     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  35-41     Citation Subset:  IM    
Dept of Internal Medicine, University Hospital Giessen and Marburg, Germany.
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MeSH Terms
Enzyme Activation
Guanylate Cyclase / metabolism*
Hypertension, Pulmonary / drug therapy*
Pyrazoles / therapeutic use*
Pyrimidines / therapeutic use*
Vasodilator Agents / therapeutic use*
Reg. No./Substance:
0/Pyrazoles; 0/Pyrimidines; 0/Vasodilator Agents; 625115-55-1/riociguat; EC Cyclase

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