Chemical called natural tranquilizer

October 23, 1992|By Jonathan Bor | Jonathan Bor,Staff Writer

The discovery of a natural chemical that sent three Italian patients into lengthy stupors might someday show scientists a different way to control such common disorders such as anxiety, panic and even epilepsy.

Dr. Jeffrey D. Rothstein, a neurologist at the Johns Hopkins School of Medicine, said yesterday that he and colleagues had identified a chemical that, in excess quantities, produced a rare disorder that caused the Italians to lapse into sleep-like trances lasting from an hour to a day a time.

They are calling the chemical, which is made somewhere in the body, endozepine. The name is a play on a group of man-made drugs -- called benzodiazepines -- that includes the well-known tranquilizers Valium and Xanax.

While too much of the natural chemical produced the sleeping disorder, it is possible that lesser quantities given in drug form could offer relief to patients suffering from anxiety and seizures.

"It normally acts to clean up or fine-tune communication between the cells," Dr. Rothstein said. "It sort of smooths things, takes the edge off a signal."

"There are hints that maybe deficiencies of these compounds may play a role in anxiety," he added. "Drug development might provide variations of this natural agent."

Making the drug in the laboratory could be years off. Dr. Rothstein said he has yet to identify the chemical's exact structure, a requirement before anyone can make a replica.

Scientists have been on the trail of the chemical since 1977, when European researchers discovered places on the surface of brain cells where tranquilizing drugs bind to deliver their effect. The discovery of the so-called Valium receptors led scientists to speculate that the brain might produce chemicals with "smoothing" effects of their own.

Dr. Rothstein said he has been studying endozepines as likely candidates for a few years. This year, he got the opportunity to test his theory when he heard Italian physicians describe the cases of the sleepy patients. What triggered his interest was the fact that the patients woke up when they were given a drug that blocks the Valium receptor.

Whatever chemical made them sleepy must have worked on the Valium receptor, he reasoned.

When the Italian doctors sent him blood and fluid samples from the patients, he found huge quantities of endozepines.

A report of the finding appears in this week's Lancet, a British medical journal. Also participating in the research were Dr. Allansandro Guidotti and Dr. Ermino Costa of the Georgetown Institute for Neuroscience, and researchers from Hoffmann-La Roche Laboratories of Nutley, N.J.

The scientists have since extracted the chemical from cows' brains. And when they artificially gave laboratory animals the type of seizures that Valium can block, the natural chemical did just as well.

"We think Dr. Rothstein and colleagues stumbled upon a very interesting finding," said Dr. Steven M. Paul, scientific director of the National Institute of Mental Health. "It could be a way of making a novel sleeping medication," which could also reduce anxiety and depression.

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