28.1 Does Thalidomide racemise in humans?
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This article is from the Chemistry FAQ, by Bruce Hamilton B.Hamilton@irl.cri.nz with numerous contributions by others.
28.1 Does Thalidomide racemise in humans?
Thalidomide ( N-phthaloyl-alpha-aminoglutarimide ) is well known as an
enantiomeric sedative-hypnotic drug that caused tragic birth defects in
the early 1960s. It has often been claimed that the defects were caused by
the presence of the other isomer in the production batches, and if the pure
enantiomer had been sold, then the tragic defects would have been avoided.
Unfortunately, thalidomide is optically unstable in solution; the pure
isomers of thalidomide racemise by the opening of the phthalimide ring, with
half-lives of 4-5 hours in buffer at pH 7.4, and less than 10 minutes in the
blood. Thus shortly after administration of either enantiomer, the other
enantiomer will be present in significant quantities [1].
Some recent work has revealed that thalidomide inhibits the production of
tumour necrosis factor alpha. Elevated levels of TNF-alpha are associated
with several inflammatory conditions. This has led to the development of
analogues that are chirally stable in reconstituted human plasma, and which
are undergoing development as anti-inflammatory drugs [2].
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