Riociguat

Drug that can be used to treat chronic thromboembolic pulmonary hypertension (CTEPH) and special forms of pulmonary arterial hypertension (PAH). Encouraging results have been obtained in systemic scleroderma. Riociguat acts as a stimulator of soluble guanylate cyclase (sGC), an important enzyme in the nitric oxide signaling pathway.

Nitric oxide (NO) acts as a signal molecule in smooth muscle cells, for the dilation of blood vessels.

In patients with pulmonary arterial hypertension (PAH), the enzyme NO synthase, which is responsible for NO production, is only present in reduced amounts. As a result, these patients have lower concentrations of cell-produced NO and vasoconstriction. NO binds as a signal molecule to the enzyme soluble guanylate cyclase (sGC) and thus induces the production of the secondary signal molecule (second messenger) cyclic guanosine monophosphate (cGMP).

Riociguat acts as a direct stimulator of guanylate cyclase independent of NO. Furthermore, riociguat acts synergistically to NO and achieves anti-aggregatory, anti-proliferative and vasodilatory effects.

1. Distler O et al (2017) RISE-SSc: Riociguat in diffuse cutaneous systemic sclerosis. Respir Med 122 Suppl 1:S14-S17.