Uetrecht J, Zahid N, Shear N H, Biggar W D
Faculty of Pharmacy, University of Toronto, Ontario, Canada.
J Pharmacol Exp Ther. 1988 Apr;245(1):274-9.
Dapsone is an effective anti-inflammatory agent in conditions in which inflammation is mediated by neutrophils. Dapsone also has been associated with agranulocytosis. We found that neutrophils, which had been activated by a phorbol ester or opsonized zymosan, oxidized dapsone to its nitroderivative. It appears as if this is due to oxidation of dapsone by myeloperoxidase to the hydroxylamine, followed by nonenzymatic oxidation of the hydroxylamine to the nitroderivative. The hydroxylamine can be isolated if ascorbic acid is added to the incubations. Monocytes also contain myeloperoxidase and activated mononuclear leukocytes also metabolize dapsone to the hydroxylamine. Dapsone also causes a mononucleosis-like syndrome. The reactive hydroxylamine could be responsible for both the pharmacologic and toxic properties of dapsone.
氨苯砜在由中性粒细胞介导炎症的病症中是一种有效的抗炎剂。氨苯砜也与粒细胞缺乏症有关。我们发现，被佛波酯或调理酵母聚糖激活的中性粒细胞将氨苯砜氧化为其硝基衍生物。似乎这是由于髓过氧化物酶将氨苯砜氧化为羟胺，随后羟胺非酶氧化为硝基衍生物所致。如果在孵育中加入抗坏血酸，羟胺可以被分离出来。单核细胞也含有髓过氧化物酶，活化的单核白细胞也将氨苯砜代谢为羟胺。氨苯砜还会引起单核细胞增多症样综合征。反应性羟胺可能是氨苯砜药理和毒性特性的原因。
