Premenstrual Disorders

Imipramine is called tricyclic because its chemical structure looks like three rings. Once scientists realized that imipramine worked to combat depression, researchers looked for other molecules that had three chemical rings, an example of homology. Many researchers, however, still believed that serotonin held the key to most mood problems. Although another new antidepressant called desipramine was developed, it affected the transmitter nor- epinephrine more than serotonin—and so the search for a drug that affected only serotonin continued. Finally, in the 1960s, Bryan Molloy, a Scottish chemist, and Ray Fuller, a pharmacologist, working together at Eli Lilly and Company, a pharmaceutical researching and manufacturing firm, used a combi- nation of studies to find the first selective serotonin reuptake inhibi- tors (SSRIs). Molloy was working on a heart regulator, while Fuller was testing new antidepressants on rats. Fuller convinced Molloy to work on chemicals that affect transmitters in the brain. Molloy be- gan by studying previous work on neurotransmitters. Because much of this work had been done using antihistamines, Molloy decided to start with them, using a model by a third researcher at Lilly, Rob- ert Rathbun. Finally, David Wong, a researcher in antibiotics, began studying the role of serotonin in mood regulation. Together, this team searched for answers to the serotonin problem in mood regu- lation. When Wong learned of the research of Solomon Snyder of Johns Hopkins University, he began using his technology on Molloy’s an- tidepressants. He quickly found that they were like drugs already available. He continued his research by testing the chemicals that had failed Molloy’s tests. One of these, a compound labeled 82816, was found to block the uptake of serotonin without affecting other transmitters. The test was run on Fuller’s rats next. From these stud- ies, Bryan Molloy and Klaus Schmiegel, another Lilly researcher, co- invented a group of synthesized compounds called aryloxphenylpro- pylamines, which includes the compound called fluoxetine oxalate. These chemicals were then made into fluoxetine hydrochloride, the active ingredient in Prozac.

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Premenstrual Disorders •