Oral agent that is a stimulator of soluble guanylate cyclase (sGC).
Half-life 5–10 hours.
Used to treat two forms of pulmonary hypertension (PH): chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH).
Can cause fetal harm and is therefore contraindicated in pregnant women.
Serious adverse effects includes bleeding, hypotension, headache, and gastrointestinal disorders.
Nitrates and phosphodiesterase inhibitors, including PDE5 inhibitors, increase the hypotensive effect, and therefore contraindicated.
Levels in the blood are reduced by tobacco smoking and strong inhibitors of the liver enzyme CYP3A4, and increased by strong cytochrome inducers.
Nitric oxide (NO) is a signalling molecule on vascular smooth muscle cells, inducing vasodilation, and binds to soluble guanylate cyclase (sGC) and mediates the synthesis of the secondary messenger cyclic guanosine monophosphate (cGMP).
The synthesised cGMP activates cGMP-dependent protein kinase to regulate cytosolic calcium ion concentration, changing the actin–myosin contractility, resulting in vasodilation.
In pulmonary arterial hypertension endothelial NO synthase, the enzyme that is responsible for the production of NO, is expressed at reduced levels and with lower levels of endothelial cell-derived NO reduced vasodilation of smooth muscle cells occurs.
NO reduces pulmonary smooth muscle cell growth, antagonizes platelet inhibition and has a role in the pathogenesis of PAH.
The sGC stimulator riociguat directly stimulates sGC activity independent of NO.
The sGC stimulator riociguat acts in synergy with NO to produce anti-aggregatory, anti-proliferative, and vasodilatory effects.
Is rapidly absorbed, and maximum plasma concentration is reached between 0.5–1.5 h.
The mean elimination half-life appears is 5–10 hours.
Plasma concentrations are variable between patients.
An open-label, non-controlled phase II trial of riociguat in 75 adult patients (42 with CTEPH and 33 with PAH, significantly improved exercise capacity and hemodynamic parameters such as pulmonary vascular resistance, cardiac output and pulmonary arterial pressure compared to baseline values.