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Hofmann, Schmofmann: Atracurium Undergoes Michael Elimination

2001; Lippincott Williams & Wilkins; Volume: 95; Issue: 1 Linguagem: Inglês

10.1097/00000542-200107000-00048

1528-1175

Theodore A. Alston,

Chemical Reactions and Isotopes

Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. talston@partners.orgTo the Editor:—Cisatracurium and atracurium are short-acting because they undergo spontaneous decomposition under physiologic conditions. We have all heard of the process termed a Hofmann elimination. In pharmacology, elimination is a mechanism of removing the active form of a drug from the body. In chemistry, elimination is a reaction giving rise to a double bond. The pharmacologic elimination of atracurium isomers happens to involve a chemical elimination reaction, but is the reaction a Hofmann elimination?Elucidating the structures of numerous alkaloids, August Wilhelm von Hofmann (1818–1892) broke down quaternary amines by heating them with a flame. Under the conditions of Hofmann, all of the neuromuscular blocking agents undergo decomposition. Clearly, the atracurium isomers possess some special chemical feature. They are unique because their nitrogenous leaving groups are situated in the “β position” with respect to a carbonyl group (fig. 1). Carbonyl compounds possess acidic α hydrogens and therefore undergo ready α,β elimination reactions. These facile reactions were first emphasized by Arthur Michael (1853–1942) and are often named after him. 1–3The term Hofmann elimination correctly indicates that atracurium is a quaternary amino compound that is transformed into a tertiary product. However, the term does not enlighten as to why the other quaternary amino relaxants do not also undergo that reaction in the body. Although the term Michael elimination would be mechanistically informative, Hofmann elimination is probably here to stay. Michael did spend some student days in the Hofmann laboratory, and perhaps Michael would not have objected to this remembrance of a mentor—maybe.