4-(AMINOMETHYL)BENZENESULFONAMIDE

Absorption

Mafenide is absorbed through devascularized areas into the systemic circulation following topical administration.

Toxicity

Since mafenide is metabolized to a carbonic anhydrase inhibitor, metabolic acidosis could occur.

Originator

Sulfamylon,Winthrop,US,1949

The Uses of 4-(AMINOMETHYL)BENZENESULFONAMIDE

antibacterial

Indications

Indicated for use as an adjunctive topical antimicrobial agent to control bacterial infection when used under moist dressings over meshed autografts on excised burn wounds.

Background

Mafenide is a sulfonamide-type antimicrobial agent used to treat severe burns. It acts by reducing the bacterial population present in the burn tissue and promotes healing of deep burns. In 1998, mafenide acetate was approved under the FDA’s accelerated approval regulations. In November 2022, the use of mafenide acetate (powder for 5% topical solution) was withdrawn by the FDA due to an unresolved confirmatory study required to fulfill the accelerated approval requirements.

Definition

ChEBI: Mafenide is an aromatic amine.

Manufacturing Process

For the preparation of mafenide 50 g of acetylbenzylamine are introduced while stirring into 150 cc of chlorosulfonic acid, whereby the temperature is kept below 40°C by external cooling. After several hours' storing at ordinary temperature the mixture is heated for 1 hour in the boiling water-bath and after cooling, poured on to ice. Thereupon the 4-acetylaminoethylbenzenesulfonic acid chloride precipitates at first in an oily form, but solidifies after short stirring to crystals. The product sucked off and washed with cold water is introduced into a 10% aqueous ammonia solution. Thereby dissolution takes place while heating and after a short time the 4- acetylaminomethyl-benzenesulfonic acid amide precipitates in a crystalline form. After heating to 70°C for 30 minutes the solution is cooled, filtered with suction and washed out. The product is obtained when recrystallized from water or dilute alcohol in colorless crystals melting at 177%. It is readily soluble in warm water, extremely readily soluble in dilute sodium hydroxide solution.

brand name

Sulfamylon (Sterling Winthrop).

Therapeutic Function

Antibacterial

Pharmaceutical Applications

p-Aminomethylbenzene sulfonamide; Sulfamylon.
A topical agent formerly used extensively in burns, especially for its action in suppressing Ps. aeruginosa. It is rapidly absorbed through burned skin and is unusual in that it is not neutralized by p-aminobenzoic acid or by tissue exudates. Disadvantages of its use are local pain and burning, a variety of allergic reactions including erythema multiforme and its capacity to inhibit carbonic anhydrase, necessitating careful observation to detect the development of metabolic acidosis. Its metabolite, p-carboxybenzene sulfonamide, also inhibits carbonic anhydrase but has no antibacterial activity. Mafenide propionate was formerly used in ophthalmic preparations.

Synthesis

Maphenide, n-(aminomethyl)-benzenesulfamide (33.1.48), is structurally somewhat different from all drugs examined above in that the amino group in the p-position to the sulfonamide group is distanced from the benzene ring by one methyl group. This drug is synthesized from N-benzylacetamide, subsequent reaction of which with chlorosulfonic acid and then with ammonia gives 4-(acetamidomethyl)-benzene-sulfonamide (33.1.47). Hydrolyzing this product with a base gives maphenid.

Synonyms of this drug are marfanil, mezudin, ambamide, septicid, and others.

Metabolism

Metabolized to a carbonic anhydrase inhibitor.