Carbon Monoxide as a Potential Therapeutic Agent: A Molecular Analysis of Its Safety Profiles.

Carbon monoxide (CO) is endogenously produced in mammals, with blood concentrations in the high micromolar range in the hemoglobin-bound form. Further, CO has shown therapeutic effects in various animal models. Despite its reputation as a poisonous gas at high concentrations, we show that CO should have a wide enough safety margin for therapeutic applications. The analysis considers a large number of factors including levels of endogenous CO, its safety margin in comparison to commonly encountered biomolecules or drugs, anticipated enhanced safety profiles when delivered via a noninhalation mode, and the large amount of safety data from human clinical trials. It should be emphasized that having a wide enough safety margin for therapeutic use does not mean that it is benign or safe to the general public, even at low doses. We defer the latter to public health experts. Importantly, this Perspective is written for drug discovery professionals and not the general public.