Mechanism of action
As an antibacterial, dapsone inhibits bacterial synthesis of dihydrofolic acid, via competition with para-aminobenzoate for the active site of dihydropteroate synthase, thereby inhibiting nucleic acid synthesis. Though structurally distinct from dapsone, the sulfonamide group of antibacterial drugs also work in this way. As an anti-inflammatory, dapsone inhibits the myeloperoxidase-H2O2-halide-mediated cytotoxic system in polymorphonucleocytes. As part of the respiratory burst that neutrophils use to kill bacteria, myeloperoxidase converts hydrogen peroxide (H2O2) into hypochlorous acid (HOCl). HOCl is the most potent oxidant generated by neutrophils, and can cause significant tissue damage during inflammation. Dapsone arrests myeloperoxidase in an inactive intermediate form, reversibly inhibiting the enzyme. This prevents accumulation of hypochlorous acid, and reduces tissue damage during inflammation. Myeloperoxidase inhibition has also been suggested as a neuron-sparing mechanism for reducing inflammation in neurodegenerative diseases such as Alzheimers disease and stroke.Dapsones anti-inflammatory and immunomodulatory effects are thought to be its mechanism of action in treating dermatitis herpetiformis.Dapsone is an odorless white to creamy-white crystalline powder with a slightly bitter taste. History
Discovery
In the early 20th century, the German chemist Paul Ehrlich was developing theories of selective toxicity based largely on the ability of certain dyes to kill microbes. Gerhard Domagk, who would later win a Nobel Prize for his efforts, made a major breakthrough in 1932 with the discovery of the antibacterial prontosil red (sulfonamidochrysoidine).
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