BAY 41-2272 is an activator of nitric oxide-sensitive guanylyl cyclase (NO-sensitive GC) with EC50 values of 0.3 μmol/L and 3 μmol/L in the presence and absence of 100 nmol/L DEA-NO, respectively [1].
NO-sensitive GC catalyzes the cGMP formation. It is generally considered as the most important receptor of the signaling molecule NO. The NO/cGMP pathway plays a role in many physiological processes such as the inhibition of platelet aggregation and the relaxation of smooth muscle [1].
In platelets, GSNO at 3 μmol/L (a submaximally effective concentration) was used to assess a possible sensitizing effect of BAY 41-2272 on NO-sensitive GC. The cGMP response resulted from the application of NO at this concentration in the absence of BAY 41-2272 was only marginal. In the presence of BAY 41-2272 at 100 μmol/L, treatment with GSNO at 3 μmol/L resulted in a rapid increase in cGMP up to 1000 pmol/109 platelets [1].
The sGC/NO system was implicated in the pathogenesis of erectile dysfunction. Intravenous treatment with BAY 41-2272 at 1 mg/kg induced only a very weak erection in rabbits, with a maximal length of exposed mucosa of about 3mm at 10 min, and the effect lasted for approximate 30 minutes. SNP is a NO donor. Simultaneous administration of SNP potentiated the effect of BAY 41-2272. Intravenous treatment with SNP at 0.2 mg/kg resulted in a short-lasting erection of about 5~10 minutes, and a peak length of uncovered penile mucosa of 5 mm. Administration with BAY 41-2272 at 1 mg/kg IV followed by SNP at 0.2 mg/kg IV 5 minutes later, resulted in lengths of ensuing erection with a mean of 15 mm, longer than lengths resulted from treatments with two compounds separately [2].
References:
[1]. Mullershausen F, Russwurm M, Friebe A, et al. Inhibition of phosphodiesterase type 5 by the activator of nitric oxide-sensitive guanylyl cyclase BAY 41-2272. Circulation, 2004, 109(14): 1711-1713.
[2]. Bischoff E, Schramm M, Straub A, et al. BAY 41-2272: a stimulator of soluble guanylyl cyclase induces nitric oxide-dependent penile erection in vivo. Urology, 2003, 61(2): 464-467.