Blogging About NO Clogging

Jan 12, 2024

Time and again in conditions like myocardial infarction, hemorrhagic/hypovolemic shock, stroke, pulmonary hypertension, heart failure, diabetes, atherosclerosis, chronic kidney disease, sickle cell disease and others, EpicentRx lead molecule, RRx-001 (nibrozetone), has demonstrated that it widens or dilates constricted and/or obstructed vasculature and prevents platelets from clumping or aggregating—in other words, it unclogs the vasculature—to increase local blood flow and oxygen delivery through the massive release of the fast acting vasoactive free radical, nitric oxide (NO).

Unlike other approved NO donors such as nitroglycerin, isosorbide mononitrate (Imdur), or sodium nitroprusside used to treat chest pain or angina, RRx-001 (nibrozetone) only releases nitric oxide under hypoxic/ischemic or low oxygen conditions—in other words, on demand, precisely where the NO is needed, and not where the NO isn’t needed—or wanted.

To our best knowledge, all other NO donors release nitric oxide not selectively or on demand like RRx-001 (nibrozetone) but systemically throughout the body—the result is that these NO donors are associated with serious symptoms such as low blood pressure (hypotension), headaches and methemoglobinemia, which interferes with the oxygen-carrying capacity of red blood cells.

By contrast, in close to 400 patients, RRx-001 (nibrozetone) has never been associated with hypotension, headaches, or methemoglobinemia—and it almost certainly never will be. The reason is related to the metabolism and disposition of RRx-001 (nibrozetone) where severely hypoxic/ischemic conditions must be present for RRx-001 (nibrozetone) to fragment and release nitric oxide.

So, is there a cardiovascular disease condition where RRx-001 (nibrozetone) would be unlikely to have therapeutic activity?

Hmmm…pun intended, but probably NO.