Drug intelligence / Profile preview

sildenafil + L-NMMA + bradykinin

Development stage
Preclinical
Lead developer
Pfizer
Modality
Peptides, Small Molecules
Administration
Intra-arterial
01

Overview

This is an experimental combination of three pharmacological agents: - **Sildenafil** is a phosphodiesterase-5 (PDE5) inhibitor that increases cyclic guanosine monophosphate (cGMP) levels, leading to smooth muscle relaxation and vasodilation. It is primarily used for erectile dysfunction and pulmonary arterial hypertension by enhancing the nitric oxide (NO)/cGMP pathway[10]. - **L-NMMA** (NG-monomethyl-L-arginine) is a non-selective inhibitor of nitric oxide synthase (NOS), reducing endogenous NO production and thus causing vasoconstriction[6][8]. - **Bradykinin** is an endogenous peptide that acts as a potent vasodilator, primarily through stimulating endothelial release of NO and prostacyclin, leading to increased blood flow[8]. The combination has been studied in vascular research settings to dissect the roles of NO-mediated pathways in vascular tone regulation. In such studies, L-NMMA blunts bradykinin-induced vasodilation by inhibiting NO synthesis; sildenafil may partially restore or modulate this response by preventing cGMP breakdown even when endogenous NO production is suppressed[6]. This combination does not represent an approved therapeutic product but rather a research tool for understanding endothelial function.

02

Targets

PDE5 (Phosphodiesterase 5A)NOS1 (nNOS)Bradykinin B2 receptor

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