Leo Sternbach (1908–2005), Lowell Randall (b. 1910)
The discovery of Librium, the first benzodiazepine, is among the most fortuitous and profitable findings in the history of drug development, although it involves as many mistaken identities as a comic opera. In 1954, the Polish chemist Leo Sternbach, working at Hoffmann-La Roche in Nutley, New Jersey, was examining compounds he had prepared twenty years earlier while a PhD student at the University of Krakow. From them, he synthesized forty new compounds that were found to be biologically inactive. The fortieth compound, however, was chemically altered and put aside. Before pitching it in 1957 during a lab cleanup, by chance Sternbach decided to send it to Lowell Randall, Roche’s Director of Pharmacology, for a battery of biological screening tests in mice and cats.
The results were startling. Like phenobarbital and meprobamate, the test compound had sedative, antiseizure, and better muscle-relaxing activity, but unlike these older drugs, the animals that received the injection remained calm and alert. With its specific “tranquilizing” effects that could not be attributed to mere sedation, relatively low toxicity, and few side effects, the newly discovered chlordiazepoxide was marketed for the treatment of anxiety in 1960 as Librium.
Librium’s financial potential was obvious, and hundreds of benzodiazepines were synthesized. Several marketed derivatives include Valium (diazepam, the most successful), Ativan (lorazepam), Dalmane (flurazepam), Halcion (triazolam), Klonopin (clonazepam), Restoril (temazepam), Rohypnol (flunitrazepam), Serax (oxazepam), and Xanax (alprazolam). Benzodiazepines relieve anxiety, cause sedation to treat insomnia, attenuate muscle spasms, suppress seizures, and possibly interfere with the formation of new memories (anterograde amnesia). Small differences exist among the drugs in their effects, with the most variation in how long they continue to work.
The great acceptance of and reliance on the benzodiazepines by physicians and patients alike led to their use over extended periods for even trivial disorders. In such cases, dependence develops and discontinuation becomes difficult, as withdrawal effects can be very severe and include convulsions.
SEE ALSO Phenobarbital (1912), Meprobamate (1955), Valium (1963), Rohypnol (1975), Xanax (1981), BuSpar (1986).
Librium was the first drug to effectively relieve stress, anxiety, and tension with minimal sedation and very low mental and physical impairments. It also became the progenitor of dozens of benzodiazepine derivatives.