Schizophrenia Drug Kills Tuberculosis Bacteria

Researchers have found that phenothiazine, a drug used to treat schizophrenia, kills the bacteria that cause tuberculosis (TB) through the inhibition of the bacterial enzyme type II NADH dehydrogenase.

In 1993 the World Health Organization declared TB a global health emergency; approximately one third of the world's population is infected, and an estimated three million die from the disease each year. Especially alarming has been the spread of drug-resistant strains of TB. By the late 1990s, scientific experts and international health officials warned that drug-resistant strains were spreading faster than had been anticipated. Some believe that unless major new treatment strategies are initiated in source countries, drug-resistant TB will eventually become epidemic even in areas with good control programs, such as Europe and the United States.

In the current study, investigators at the University of Pennsylvania School of Medicine (Philadelphia, USA) used the anti-schizophrenia drug phenothiazine to treat Mycobacterium tuberculosis bacteria growing in culture and to treat mice that had been infected with the bacteria. They reported in the March 14, 2005, online edition of the Proceedings of the [U.S.] National Academy of Sciences that several phenothiazine analogs were potent killers of tuberculosis bacteria in culture and suppressed bacterial growth in a mouse model of acute infection. The target of the drug was found to be the enzyme type II NADH dehydrogenase.

"What we have now is a new target in TB,” said senior author Dr. Harvey Rubin, professor of medicine at the University of Pennsylvania School of Medicine. "We have been able to find at least the beginnings of a class of compounds that we can start working with and that we know is biochemically active against the TB bacteria in culture and in small animals. We discovered that if you inhibit the very first enzyme in the chain, you inhibit everything else downstream and eventually the bacteria die.”



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