MK-8150

MK-8150 is a novel nitric oxide donor developed as an orally available, once-daily treatment for hypertension. Its mechanism of action involves the release of nitric oxide (NO) through metabolism by the enzyme Cytochrome P450 3A4 (CYP3A4), which activates Soluble guanylate cyclase (sGC) and increases cyclic GMP (cGMP) levels, leading to vasodilation and blood pressure reduction. MK-8150 was designed to overcome nitrate tolerance commonly seen with traditional NO donors by utilizing a unique metabolic pathway. Preclinical studies demonstrated robust and sustained blood-pressure lowering in animal models, while early clinical trials in humans showed significant reductions in systolic blood pressure for up to 14 days. However, longer-term studies revealed that tolerance still developed after 28 days of dosing. The drug was safe and well tolerated but its development was discontinued due to loss of efficacy over time[1][2][3][8].