Psychotropic Drug Discovery in the 1950s: Key Breakthroughs

Introduction: Drug Discovery and Fortunate Circumstances

There is reason to believe that drug discoveries are often the result of a fortunate set of circumstances that allow a researcher to encounter a combination of substances producing exactly the effect sought at the outset. While this was largely the case a few centuries ago, things changed considerably in recent decades as society became actively involved in promoting pharmaceutical research and in supporting the individuals responsible for it. One of the best examples of drug discovery accompanied by widespread public support is the 1950s wave of psychotropic drug discoveries. A great many drugs from this period came to play an important role in society, given that they have been widely used in the decades since.

A number of drugs were discovered as a result of researchers working with natural products and exploiting specific substances those products contained. Fungal sources in particular proved especially effective in enabling scientists to synthesize certain compounds and to create therapeutic agents. The complexity of drug creation is remarkable, as there are numerous ways in which a scientist can fail and equally numerous ways in which he or she can succeed in producing the intended product. As noted by Milkman and Wanberg, "Albert Hofmann, the Swiss chemist who isolated the active ingredient in magic mushrooms, also synthesized LSD (lysergic acid diethylamide) from compounds that he isolated from ergot, a fungus that grows on rye grass" (128).

Chlorpromazine and the Dopamine Revolution

Chemists with access to innovative laboratories were able to play an active role in creating drugs that are, to a certain degree, responsible for helping society as a whole experience faster progress. Chlorpromazine is a positive example of a drug that successfully helped individuals suffering from psychiatric disorders. Marketed as Thorazine, the drug was first produced at Rhône-Poulenc, a French chemical and pharmaceutical company. From the very first tests it was subjected to, it became clear that the substance had a positive effect in calming psychotic patients. As Li and Corey observe, "Chlorpromazine also helped bring about a revolution in our understanding of the central nervous system through research into the drug's mechanism of action" (246).

The drug was especially important because of how it emphasized the significance of the neurotransmitter dopamine. The public was effectively provided with the opportunity to gain a more complex understanding of drugs that have a neurological effect. Numerous disorders could be treated with these substances, and individuals who had previously struggled to control their lives gained new possibilities. The discovery of Librium and then Valium during the 1950s and 1960s, respectively, further contributed to society's understanding of biological treatment methods for mental disorders. Antipsychotic drugs are generally aimed at helping individuals suffering from mental disorders experience fewer problems as a result of their conditions, and in many cases these patients become able to integrate into society normally and to perform tasks they would not otherwise manage.

Leo Sternbach and the Development of Benzodiazepines

One of the most intriguing aspects of any drug is the process of its discovery. Many of the individuals who discovered psychotropic drugs during the 1950s were initially interested in creating substances with entirely different effects and for a different market from the one those drugs ultimately came to serve. With numerous minor tranquilizers of the 1950s producing side effects that made it difficult for doctors to continue prescribing them, Dr. Leo Sternbach turned his attention to a new class of substances that had been relatively ignored at the time. He had previously worked with benzheptoxdiazines but had not conducted in-depth study of those compounds because he lacked the financial support to pursue them further.

Becoming an employee of Hoffmann-La Roche laboratories in New Jersey changed his perspective and enabled him to develop a series of drugs that came to be appreciated for their benefits in patients suffering from disorders such as anxiety. Sternbach submitted 26 benzheptoxdiazines for pharmacological testing, and one of the last compounds to be tested proved especially effective in achieving the effects Hoffmann-La Roche was seeking. The substance came to be called Librium, and it was observed to have powerful hypnotic effects in mice, suggesting it could be used to treat individuals with anxiety or depression. As Ramchandani notes, "Time was now ripe for clinical trials after more detailed pharmacological and toxicity studies had been performed. In 1958 the compound Ro 5-0690 (methaminodiazepoxide or chlordiazepoxide) was administered to geriatric patients in relatively large doses and found to be primarily sedating."