A Comprehensive Monograph on Coenzyme M (Mesna): From Biochemical Cofactor to Clinical Uroprotectant

Executive Summary

Coenzyme M, known pharmacologically by its generic name Mesna, is a small molecule synthetic thiol compound identified chemically as 2-mercaptoethanesulfonic acid.[1] Its application in modern medicine represents a significant achievement in targeted supportive care, particularly in oncology. The primary and critical clinical function of Mesna is the prophylaxis of hemorrhagic cystitis, a severe and dose-limiting toxicity induced by the oxazaphosphorine class of chemotherapeutic agents, which includes ifosfamide and high-dose cyclophosphamide.[1]

The pharmacological utility of Mesna is predicated on a unique and elegant mechanism of "regional detoxification." Following administration, the active Mesna is rapidly oxidized in the systemic circulation to its inactive disulfide metabolite, dimesna. This inactive form is then filtered by the kidneys and subsequently reduced back to active Mesna within the renal tubules. This process delivers a high concentration of the active, free-thiol compound directly to the bladder, where it is needed most. Here, it chemically neutralizes acrolein, the primary urotoxic metabolite of oxazaphosphorine chemotherapy, forming a stable, non-toxic conjugate that is safely excreted.[3] This pharmacokinetic-driven localization minimizes systemic interactions while maximizing protection at the target site.