Acetaminophen poses a pain-relief puzzle. Despite sharing some properties with conventional nonsteroidal anti-inflammatory drugs, such as aspirin, it doesn't inhibit cyclooxygenase (Cox) -1 or -2. Three years ago, researchers postulated that acetaminophen might inhibit Cox-3 – a Cox-1 splice variant.1 Since then, however, research into Cox-3 failed to generate much consensus. "The scientific community was very enthusiastic at the beginning," says Bela Kis of Wake Forest University. But that excitement has faded. Some continue to probe Cox-3, however, hoping the molecule may provide clues for conditions including Alzheimer disease and some cancers as well as offer some new physiological insights.

Even the name is controversial. Several researchers believe that Cox-3 should be reserved for the product of a third independent COX gene. Kis prefers the term Cox-1b, even though, he says, it doesn't seem to show Cox activity. Indeed, Kis' group found that Cox-1b shows an entirely...

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