zamicastat + sildenafil

Zamicastat + sildenafil is an investigational oral combination of two small molecule drugs: zamicastat, a potent and selective dopamine beta-hydroxylase (DBH) inhibitor, and sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor. Zamicastat inhibits norepinephrine synthesis by blocking DBH, which may modulate sympathetic activity and vascular tone, investigated primarily in hypertension, heart failure, and pulmonary arterial hypertension (PAH)[2][4][6][8]. Sildenafil increases intracellular cGMP by inhibiting PDE5, resulting in vasodilation and reduced pulmonary vascular resistance, widely used in PAH and erectile dysfunction[1][3][4][6]. Preclinical and early clinical studies indicate that the combination may have additive or synergistic effects in reducing pulmonary hypertension and preventing vascular remodeling, acting via complementary pathways that modulate cGMP and catecholamine-mediated signaling. The combination is being studied for PAH, with orphan drug designation in this indication[6][8]. No approved product currently exists for the zamicastat + sildenafil combination, and clinical development is ongoing.

Other names

zamicastatsildenafil