Riociguat-13C-d3 is intended for use as an internal standard for the quantification of riociguat by GC- or LC-MS. Riociguat is a stimulator of soluble guanylate cyclase (sGC).1,2 It stimulates recombinant sGC in a concentration-dependent manner in vitro by up to 73-fold when used at a concentration of 100 μM and by up to 112-fold when used in combination with the nitric oxide (NO) donor DEA NONOate .1 It has no effect on phosphodiesterases PDE1-9 and PDE11 when used at concentrations up to 3 μM. Riociguat (1 and 10 mg/kg) reduces pulmonary and systemic arterial pressure in a rabbit model of acute pulmonary arterial hypertension (PAH) induced by U-46619 . It also inhibits increases in right ventricular systolic pressure, right heart hypertrophy, and pulmonary artery muscularization in hypoxia-induced mouse and monocrotaline-injected rat models of chronic PAH when administered at a dose of 10 mg/kg. Formulations containing riociguat have been used in the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) and PAH.
1.Schermuly, R.T., Stasch, J.P., Pullamsetti, S.S., et al.Expression and function of soluble guanylate cyclase in pulmonary arterial hypertensionEur. Respir. J.32(4)881-891(2008) 2.Stasch, J.P., Pacher, P., and Evgenov, O.V.Soluble guanylate cyclase as an emerging therapeutic target in cardiopulmonary diseaseCirculation123(20)2263-2273(2011)