The Molecular Toxicology of Acetaminophen

Abstract

The history of the development of the analgestic drug acetaminophen is reviewed with an emphasis on the characteristics of its overdose toxicity. The P450-catalyzed oxidation of acetaminophen generates a reactive electrophile that binds covalently to proteins. Involvement of specific P450 enzymes in acetaminophen toxicity can be probed by experiments with knock-out mice. The identification of specific target proteins may help to clarify the mechanism of acetaminophen hepatoxocity.

Key Words :

• Actaminophen
• hepatotoxicity
• covalent binding
• P450

Notes

¹A few years later, another Bayer chemist, Felix Hoffmann, acetylated salicylic acid to produce acetylsalicylic acid—Bayer “Aspirin.”

²von Mering is also remembered for his discovery that diabetes can be induced in dogs by removing the pancreas.

³Additional sources: NIH: http://history.nih.gov/exhibits/bowman/BioBrodie.htm; International Society for the Study of Xenobiotics: http://www.issx.org/hissept.html.

⁴The term “nonsteroidal” distinguishes them from the anti-inflammatory steroids, such as hydrocortisone.