Nathan S. Kline (1916–1982)
With the realization that isoniazid had revolutionized the treatment of tuberculosis (TB), scientists at Hoffman La Roche Laboratories altered its chemistry in efforts to find a comparable drug. The most promising of these new compounds was iproniazid. Early trials were conducted on patients at Sea View Tuberculosis Hospital in New York, which, when it opened in 1912, was considered the finest TB hospital in the country.
The results were dramatic. TB hospitals were not known for their joyful ambience in 1952, yet, after receiving iproniazid, the patients were clearly happy, with robust appetites leading to weight gain. They were even photographed dancing! Lung x-rays failed to show any improvement in their TB, however, and trials ended when the drug was found to cause disturbing side effects, including excessive stimulation.
In unrelated laboratory tests conducted in 1952 by E. Albert Zeller at Northwestern University Medical School, iproniazid was found to block monoamine oxidase (MAO), an enzyme normally responsible for inactivating norepinephrine and serotonin. When MAO is blocked, there is a resulting increase in the levels of these neurotransmitter compounds in the brain.
THE FIRST ANTIDEPRESSANT. In the mid-1950s, newly available drugs treated schizophrenia and anxiety but not depression. Nathan S. Kline, Director of Research at Rockland State Hospital, was aware of Zeller’s findings and theorized that iproniazid, an MAO inhibitor, might have potential as an antidepressant. In 1957, Kline administered the drug to fourteen depressed patients and obtained favorable results in twelve. The psychiatric community enthusiastically embraced iproniazid (Marsilid) as a psychic energizer (Kline’s term). The glow dimmed in 1961, when the drug was withdrawn from the market after its use was associated with fifty-four fatalities caused by liver toxicity. The search was on for a safe(r) MAO inhibitor.
SEE ALSO Neurotransmitters (1920), Streptomycin (1944), Isoniazid (1951), Monoamine Oxidase Inhibitors (1961), Prozac (1987).
Depression is the most common mental-health disorder affecting teens in the United States, and suicide is one of the leading causes of death among American high school students. Iproniazid, an MAO inhibitor, was among the first widely used antidepressants.