Dapsone - Mechanism

Mechanism

As an antibacterial, dapsone inhibits bacterial synthesis of dihydrofolic acid, via competition with para-aminobenzoate for the active site of dihydropteroate synthetase. Though structurally distinct from dapsone, the sulfonamide group of antibacterial drugs also work in this way.

When used for the treatment of skin conditions in which bacteria do not have a role, the mechanism or action of dapsone is not well understood. Dapsone has anti-inflammatory and immunomodulatory effects, which are thought to come from the drug's blockade of myeloperoxidase. This is thought to be its mechanism of action in treating dermatitis herpetiformis.

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 a reducing inflammation in neurodegenerative diseases such as Alzheimer's disease and stroke.

Though dapsone is an anti-inflammatory agent and not a steroid, it does not fit the usual definition of an NSAID. By definition, NSAIDs block cyclo-oxygenase as their primary mechanism of action, which dapsone does not do.