Riociguat, an oral soluble guanylate cyclase stimulator for the treatment of pulmonary hypertension.
Pulmonary arterial hypertension (PAH) is a severe, progressive and often fatal disease for which only a limited number of drugs have proven to be of clinical benefit. One of the therapeutic approaches for this disease is the induction of pulmonary vasodilation via stimulation of the nitric oxide (NO)-mediated pathway. Abnormalities in the NO/soluble guanylate cyclase (sGC) axis and enhanced PDE5 activity render currently available drugs ineffective in many patients with PAH. Bayer AG is developing riociguat, an oral sGC stimulator, for the potential treatment of patients with PAH. Treatment with riociguat abrogated the severity of pulmonary hypertension in rodent models of the disease. Published data from phase I and II clinical trials demonstrated that riociguat was well tolerated, with single doses significantly decreasing pulmonary arterial pressure and increasing cardiac output and physical-exercise tolerance in patients with PAH. A decrease in systemic arterial diastolic pressure was the only significant side effect reported. Ongoing phase II and III trials for riociguat have been designed to address the long-term safety and clinical effectiveness of the drug in different types of pulmonary hypertension. Should the results of these trials demonstrate that riociguat is superior to current therapies, such as cyclic AMP-dependent drugs and endothelin receptor antagonists, the drug could become the preferred pharmacological treatment for patients with PAH.
Belik
Jaques
J
University of Toronto, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada. jaques.belik@sickkids.ca
D000818:Animals; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical; D002986:Clinical Trials as Topic; D003971:Diastole / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D015394:Molecular Structure; D011720:Pyrazoles / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D018160:Receptors, Cytoplasmic and Nuclear / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000071756:Soluble Guanylyl Cyclase; D013329:Structure-Activity Relationship; D013607:Tablets; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D011720:Pyrazoles; D011743:Pyrimidines; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D013607:Tablets; D014665:Vasodilator Agents; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; C542595:riociguat