Word: serotonin
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More than a bit. In fact, the entire history of serotonin and of drugs that affect it has been largely a process of trial and error marked by chance discoveries, surprise connections and unanticipated therapeutic effects. The chemical was not even first discovered in the brain. It was stumbled on in the late 1940s by U.S. and Italian researchers, working independently, in blood platelets and in the intestines, respectively. The Italians called it enteramine, the Americans serotonin (sero for blood, tonin for muscle tone)--and when the two groups compared notes, they found their compounds were identical...
...first, the effects of serotonin seemed confined to the body alone: it was found to trigger contractions in the muscles and intestines and to regulate blood pressure by forcing blood vessels to constrict. But experiments at the National Institutes of Health in the 1950s revealed that compounds that depressed serotonin levels depressed patients as well. Not long after, researchers found two more clues to the serotonin-depression connection. The first was that reserpine, an anti-blood-pressure medicine that depresses serotonin levels, can sometimes trigger depression. The second came from iproniazid, originally developed as an anti-tuberculosis agent. The medicine...
...have subsequently learned, monoamine oxidase's job is to destroy leftover neurotransmitters that are floating around loose after they have done their work. By inhibiting the action of monoamine oxidase, drugs like iproniazid let neurotransmitters circulate and keep stimulating neurons longer than they normally would. An extended soaking in serotonin and norepinephrine evidently made for a happier patient, and MAO inhibitors became the first antidepressants...
...class of antidepressants emerged. By tinkering with the chemical structure of antihistamines, a Swiss psychiatrist, Ronald Kuhn, created a drug called imipramine, first of the so-called tricyclic antidepressants. At the time no one had any idea why these medicines worked. Researchers have since learned that they keep excess serotonin and other neurotransmitters from being reabsorbed into the nerve cells they originally came from: same extended neurotransmitter bath as the MAO inhibitors, different mechanism...
Both types of antidepressant had major side effects, though, including profound drowsiness and heart palpitations. The reason, scientists generally agreed, was that they affected brain chemistry too broadly. The research seemed to point to serotonin as the most important mood-enhancing chemical, though not the only one, and so neurochemists set about looking for a drug that would boost the influence of serotonin alone. In 1974, after a decade of work, Eli Lilly came up with Prozac, first of the so-called selective serotonin reuptake inhibitors, or SSRIS, and it was finally approved...