Acetaminophen (621) has found increasing use as a substitute for acetyl-salicylic acid as a mild pain-killer. The mechanism of action of acetaminophen is unknown (Clissold, 1986). Acetaminophen reduces the hydroperoxide levels in tissues. Since cyclooxygenase is activated by hydroperoxides, Lands (1981) suggested that acetaminophen could indirectly reduce prostaglandin synthesis. However, many other reducing agents do not share the pharmacological effects of acetaminophen. More recently, Vane (1994) suggested that a third isozyme of cyclooxygenase ("COX3"), located in the brain, might be inhibited by the agent. Acetaminophen does not inhibit lipoxygenases, but Su et al. (1995) found that the drug potently inhibited linoleic acid dioxygenase, a fungal enzyme. Whether the drug also inhibits oxygenation of polyunsaturated fatty acids in humans remains to be determined.

Fast flow systems have enabled the detection of the 4-acetamidophenoxyl radical, a species believed to be an important metabolic intermediate in the activity and toxicity of this drug (Fischer et al., 1986). The effect of acetaminophen on the respiratory burst of isolated human polymorphonuclear leukocytes (PMNLs) has been studied. The drug inhibited the chemiluminescence peak response of cells stimulated with PMA or opsonized zymosan in a concentration-dependent manner. Generation of superoxide

Was this article helpful?

0 0

Post a comment