# "The Big Sleep" by Ian Parker

I have known many chemists who have been involved in the synthesis of potential therapeutics and have learned quite a bit about the process from the view of those in the laboratory, including some of our graduates.  Before that promising candidate can begin to earn back the investment in chemistry that discovered it, there is a long process of clinical trials resulting (sometimes) in eventual FDA approval.  In this fairly lengthy New Yorker article, Ian Parker recounts the saga of Suvorexant, a potential rival of Lunesta (eszopiclone), and Ambien (zolpedem), which have largely replaced the previous blockbusters, Librium, Valium, and the benzodiazepines Dalmane and Halcion.  All of these drugs apparently work by attaching to GABA (gamma-amino butyric acid) receptors in the brain.  Most of these drugs were developed through what is basically a trial-and-error approach, but Suvorexant was the result of "rational design", starting with knowledge of the GABA receptor and synthesis of structures that molecular modeling predicted would bind.  This informative history of  the quest for more effective (and highly profitable) sleep promoters with fewer side effects beings largely after the chemistry is done, and leads us through the clinical testing and approval process, Spoiler Alert – the ending is only a partial victory for Merck and rational design.

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Publication Date:
Wednesday, December 11, 2013
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Hal Harris
University of Missouri - St. Louis