Premenstrual Disorders

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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.