Dr. Frank M. Berger, 94; creator of tranquilizer Miltown, which inaugurated age of mood-changing drugs

Dr. Frank M. Berger, the psychiatrist who jump-started the modern age of mood-changing drugs with the discovery of the tranquilizer Miltown, died Sunday after suffering a heart attack at his home in New York. He was 94.

Berger was an anonymous researcher in the Yorkshire, England, laboratories of British Drug House Ltd. when he noticed that a chemical he was working with, myanesin, had a tranquilizing effect on laboratory animals – calming their jitters, rendering them insensitive to pain and preventing them from returning upright when they were placed on their backs.

He and his colleagues described the short-lived effects in a 1946 report in the British Journal of Pharmacology that is now considered a classic.

His employer chose to let the discovery slide, but Berger kept thinking about it. After he became director of research at Wallace Laboratories in Cranbury, N.J., he and chemist Bernard J. Ludwig synthesized a series of compounds closely related to myanesin.

One of them was meprobamate.

A study of 101 patients at the Mississippi State Hospital in Whitfield showed that 3% given the drug made a complete recovery, 29% were greatly improved and 50% were somewhat better.

Again, his employer failed to see a potential benefit from the compound. But this time, Berger decided to take matters in his own hands.

He and his colleagues made a short film about the effects of the drug on rhesus monkeys and played it for a group of physicians in San Francisco. That created enough interest in the compound that Wallace, a subsidiary of Carter Products, brought it to market in May 1955, naming it Miltown after the nearby village of Miltown, N.J. They also licensed rights to the drug to Wyeth Inc., which sold it under the name Equanil.

Before then, the only drugs available for treating mood disorders were barbiturates, powerful depressants that were addictive and had dangerous side effects.

Miltown was perceived to have none of those problems and it was an immediate hit, quickly becoming the best-selling drug that had ever been introduced in the United States and overwhelming the two companies’ ability to produce it.

It became a favorite among intellectuals and celebrities, especially Hollywood types, who promoted its use enthusiastically. Television comedian Milton Berle, for example, frequently called himself “Miltown Berle.”

A February 1956 report in Time magazine noted that a drugstore at Sunset and Gower “splashed huge red letters across its window when a shipment arrived ‘Yes, we have Miltown.’ ” Schwab’s drugstore had dispensed a quarter of a million pills in four months from its four stores and had turned away more prescriptions than it had filled.

Within a year after Miltown’s release, an estimated 5% of Americans were taking tranquilizers.

Other pharmaceutical companies were quick to jump on board. In 1960, the Swiss company Hoffman-LaRoche introduced Librium. Three years later, it brought out Valium, which was more powerful and could be given in smaller doses.

Today, drug companies spend hundreds of millions of dollars looking for the next big psychoactive chemical.

By the time Valium was released, it was becoming recognized that Miltown was not as benign as had been thought. In 1965, experts ruled that it should be classed as a sedative rather than a tranquilizer.

About the same time, researchers concluded that it could become addictive at doses not much above the recommended levels. By 1970, it was placed on Schedule IV of the Convention on Psychotropic Substances, making it a controlled substance, limiting its use and necessitating precise records on production and distribution.

Berger later conceded the problems with overdoses, but told the New York Times, “One just expects it will be used properly. There is no warning on scalpels, ‘This is sharp, don’t cut yourself.’ ”

Berger subsequently invented a number of other drugs, including the muscle-relaxant mephenesin, the pain reliever carisoprodol (brand-named Soma) and the epilepsy drug felbamate (brand-named Felbatol), as well as a method for purifying penicillin. None of those drugs had the success – or notoriety – of Miltown, however.

Frank Milan Berger was born June 25, 1913, in Pilsen, West Bohemia, now part of the Czech Republic. He received his medical degree from the University of Prague in 1937 and worked in that country until the outbreak of World War II, when he and his wife, the former Bozena Jahodova, emigrated to England.

In 1947, they moved to the United States, where he became an assistant professor of pediatrics at the University of Rochester. He earned a second medical degree from the State University of New York in 1948 and became a U.S. citizen in 1953.

In 1949, he joined Wallace, subsequently being promoted to vice president and president. He left Wallace in 1974 to become a professor of psychiatry at the University of Louisville, where he stayed until his retirement in 1990.

His wife Bozena died in 1972. In 1975, he married Alma Christine Spadi.

In addition to his wife, he is survived by two sons, Franklin Milan Berger of New York and Thomas Jan Berger of London; a stepson, Harry Thomas Bath of Fort Collins, Colo.; two step-grandchildren; and a sister, Eva Pololi of London.

thomas.maugh@latimes.com