Psychology

Before these specialists existed, drug discovery depended entirely on serendipity. For example, the antituberculosis agent Iproniazid produced unexpected mood elevation in tuberculosis patients. Following up on this finding in 1957, scientists discovered that this drug did indeed have antidepressant efficacy in psychiatric patients. Thus, the first monoamine oxidase inhibitor was introduced to psychiatry. In the early 1950s, the Swiss psychiatrist Roland Kuhn investigated several agents chemically similar to Thorazine, a drug that had just been discovered to be effective in the treatment of schizophrenia. He was looking for a treatment for depression, and after treating his first three cases in 1956; he discovered the first tricyclic antidepressant, imipramine (Tofranil), a close chemical cousin of Thorazine. John Cade, an unknown Australian psychiatrist who had no research training, was investigating the effect produced by injecting the urine of manic patients into guinea pigs. He chose to dissolve the urine’s uric acid in water by combining it into guinea pigs, lithium made the urine less toxic, so he became interested in studying lithium itself. He found that lithium carbonate injected into guinea pigs made them lethargic. Next, he tried lithium in ten manic patients in 1948 and found their excitement to be controlled.

In the last twenty years, antidepressants have begun to be designed based on neuroscience, rather than discovered by chance. Thus, cleaner drugs affecting only serotonin have been developed, producing many fewer side effects than the older antidepressants, which affected a variety of neurotransmitters, some of which were irrelevant to their clinical effect. Progress in designing new antidepressants is slow, because the brain contains about 10 billion cells, and more than fifty known neurotransmitters along with many unknown others, which influence many targets and produce varying effects on cell genes. In spite of this extraordinary complexity, progress is being made. Once the drug is designed, the gradual process of careful testing begins. It was fifteen years from the development of Prozac in 1972 by the scientists of Eli Lilly to its release by the U.S. Food and Drug Administration for public use in 1987.