Nelociguat is a stimulator of soluble guanylate cyclase (sGC) and an active metabolite of riociguat .1,2 It is formed from riociguat by the cytochrome P450 (CYP) isoform CYP1A1.3 Nelociguat increases phosphorylation of the protein kinase G (PKG) substrate vasodilator-stimulator protein (VASP) in isolated rat aortic smooth muscle cells (EC50 = 353 nM).1 It induces vasodilation in rat aortic rings (EC50 = 75 nM). Nelociguat (3 mg/kg) decreases urine output and cardiac hypertrophy, as well as improves survival, in spontaneously hypertensive stroke-prone rats fed a high-salt high-fat diet. It improves erectile responses to electrical stimulation of the cavernous nerve in a rat model of cavernous nerve crush injury when administered at doses of 0.03 and 0.3 mg/kg.2
1.Costell, M.H., Ancellin, N., Bernard, R.E., et al.Comparison of soluble guanylate cyclase stimulators and activators in models of cardiovascular disease associated with oxidative stressFront. Pharmacol.3128(2012) 2.Oudot, A., Behr-Roussel, D., Poirier, S., et al.Combination of BAY 60-4552 and vardenafil exerts proerectile facilitator effects in rats with cavernous nerve injury: A proof of concept study for the treatment of phosphodiesterase type 5 inhibitor failureEur. Urol.60(5)1020-1026(2011) 3.Hlo?ek, T., ?tícha, M., Bursová, M., et al.Sensitive CE-MS method for monitoring of riociguat and desmethylriociguat levels in human serumElectrophoresis41(18-19)1564-1567(2020)