The expanding role of benzodiazepines in neurology: an historical overview
Elaine Wyllie, MD
Head, Pediatric Epilepsy Program, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195-5221
THE BENZODIAZEPINES have been an important part of the neurologist’s armamentarium since the 1960s and, as new compounds become available, their therapeutic role continues to expand. Sleep disorders, movement disorders, epilepsy, and psychiatric conditions are among the problems for which benzodiazepines may be helpful. The purpose of this volume is to focus attention on the rational use of these medications in this diverse group of disorders.
The “father” of the benzodiazepines is Dr. Leo H. Sternbach of the Medicinal Chemistry Research Department of Hoffmann-La Roche Incorporated in Nutley, New Jersey (Figure 1). Dr. Sternbach began his research on the parent group of compounds—a class of heterocycles (Figure 2)—at the University of Cracow in Poland in 1933.1 He stated that he was attracted to these compounds, known since 1891, because of their relative accessibility, easy crystallization, and the expectation that they would lend themselves to many variations and transformations.1 Dr. Sternbach’s investigations were interrupted by World War II; but when resumed in 1955 with Hoffmann-La Roche, they were extremely fruitful.
In a retrospective of his work, Dr. Sternbach explained that his initial experiments, adding basic side chains, resulted in compounds with “uninteresting” pharmacologic properties.1 However, treatment with methylamine produced compounds with muscle-relaxant, taming, sedative, and anticonvulsant effects. Further experimentation resulted in the so-called “meth-ylamino derivative II” (Figure 3), which progressed in 1957 toward clinical trials as an anxiolytic. In 1960, Dr. Sternbach simplified this derivative compound for enhanced pharmacologic properties and reduced bitterness, thus introducing the drug chlordiazepoxide (Librium). . .