'Designer Drug' Linked to Parkinson's

At least 400 northern California drug abusers appear to have taken a synthetic form of the drug Demerol which can destroy a portion of the brain and cause Parkinson's disease in young people.

Newer versions of the drug -- which may also prove poisonous -- are still being produced in clandestine laboratories, said Dr. A. James Ruttenber, an epidemiologist with the Centers for Disease Control in Atlanta.

The drug may be spreading to other parts of the country, Ruttenber says. Materials and instructions for making the synthetic drugs were found in two clandestine labs in San Diego and one in Brownsville, Tex.

Ruttenber reported the CDC's preliminary findings at the first national "Symposium on MPTP" last week at the Uniformed Services University of Health Sciences in Bethesda.

MPTP, which comes from the same family of drugs as Demerol, caused an epidemic of Parkinson's disease among young drug addicts in the San Francisco Bay area after it was sold as a synthetic heroin in 1982. Its discovery caused an explosion of research into the cause and basic neurology of Parkinson's disease, a degenerative syndrome that strikes people in their fifties and sixties. It causes slowed movement, tremor, rigidity, dementia and death. There is no cure, although the symptoms can be relieved with a drug called L-dopa.

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A similar epidemic struck narcotics abusers in the Netherlands in late 1981 and early 1982. Forty-three developed symptoms; 11 died.

The MPTP experience in California and that of another synthetic heroin called fentanyl also has focused federal attention on trying to find a way to stop clandestine laboratories from producing so-called "designer drugs."

Currently, it is legal to make drugs like MPTP because the underground chemists design them to be slightly different from related drugs which are regulated, said Miriam Davis, an adviser to the assistant secretary for health in the Department of Health and Human Services. The modified versions remain similar enough to the active, regulated drugs to produce a narcotic effect.

Entire families of related drugs have not been regulated because "we were concerned about the effects on basic research and on drug research, both in industry and the university," Davis said. But new legislation is now being developed "that would prohibit designer drug manufacture and at the same time not inhibit research or drug and chemical manufacture," Davis said. She declined to describe the legislation because it currently is being reviewed by HHS and the Department of Justice, but she did say it could be introduced in Congress as early as this summer.

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The MPTP story, which began in 1982, is an example of the dangers caused by designer drugs. An underground San Francisco Bay area drug laboratory was making a synthetic drug similar to Demerol when the chemical reactions went awry and produced MPTP as a contaminating byproduct. Since these labs don't perform quality control tests, the drug, containing the MPTP contaminant, was sold on the street.

The effects of MPTP damage were first discovered in July of that year when county sheriffs carried a paralyzed, 42-year-old heroin addict from jail to the Santa Clara Valley Medical Center in San Jose. While awaiting a hearing, the man had slowly lost his ability to move. Over the next weeks, six more similarly paralyzed drug users were discovered.

Dr. J. William Langston, the medical center's chief of neurology, saw the paralyzed addicts and through a series of lucky breaks and persistent detective work, determined -- with the help of Stanford University chemist Ian Irwin -- that the compound MPTP had damaged the brain.

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The first known case of MPTP poisoning occurred in 1976 when a Bethesda college student made synthetic drugs in his basement for personal use. He, too, apparently produced MPTP as a contaminant and developed the symptoms of Parkinson's disease. He killed himself before National Institutes of Health researchers were able to identify the drug.

Once Langston realized that MPTP produced brain damage similar to Parkinson's disease, he used L-dopa to reverse the paralysis of the California addicts.

A few months later, Dr. R. Stanley Burns, a neurologist at the National Institute of Mental Health, showed that MPTP caused a Parkinson's-like condition in monkeys and created the first animal model for the disease.

While the discovery of MPTP has not provided a new treatment for Parkinson's disease, it has suggested a possible cause.

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Langston and Dr. Donald B. Calne from the University of British Columbia in Vancouver suggested that Parkinson's disease may be caused by an environmental chemical similar to MPTP.

Langston and Calne hypothesize that the toxin kills some of the brain, but does not produce Parkinson's until aging naturally eliminates key remaining nerve cells gradually. When fewer than 20 percent of those nerves remain, the person develops the disease.

No MPTP-like environmental contaminant has yet been found, although several laboratories are now looking. Other researchers, however, have expressed doubt that Parkinson's is caused by environmental chemicals similar to MPTP.

Langston and Calne are now trying to test their hypothesis by sending California addicts -- both the original seven who were paralyzed and others identified by the CDC -- to Vancouver, where Calne's group can study the dopamine distribution in their brains with Positron Emission Tomography (PET).

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The initial scans show that dopamine distribution is equally reduced in the brains of both drug addicts and older Parkinson's patients.

Calne's group plans to scan the brains of the California drug addicts -- both the severely damaged and those who have no symptoms but who used MPTP -- on a regular basis for several years, perhaps decades, to determine whether their brains continue to lose dopamine and develop Parkinson's. If that occurs, it will strengthen the environmental cause hypothesis.

CDC's Ruttenber said his group is trying to get institutional support to follow these damaged addicts "for the rest of their lives. . . . It is going to be expensive, but if you are doing all this research on animal models, and you don't know what the natural history of the disease is, you are going to be lost."

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Much of the recent research reported during last week's symposium tried to explain why MPTP poisoned the brain and how it selectively killed the dopamine-producing cells associated with Parkinson's disease.

Researchers now believe that MPTP itself is not poisonous, but that the brain converts it into MPP-plus, an extremely toxic compound similar to paraquat, a herbicide used to destroy marijuana plants and which causes lung damage when contaminated marijuana is smoked. Reportedly, MPP-plus was once tested as an herbicide.

An enzyme call monoamine oxidase (MAO) controls the conversion of MPTP to MPP-plus. By blocking the MAO enzyme with another drug, monkeys experimentally injected with MPTP could be protected from its ill effects.

Dr. Joussa B.H. Youdim from the Technion-Israel Institute of Technology in Haifa, Israel, reported on a study at the Lainz Hospital in Vienna, Austria, that showed Parkinson's patients lived 15 months longer and their disease progressed more slowly when they received the MAO inhibitor deprenyl.

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A number of researchers cautioned that the Vienna study was not a controlled trial. "I think that particular piece of work is fascinating, but not entirely convincing," said Dr. C. David Marsden, chairman of neurology at the Institute of Psychiatry, Kings College Hospital, London. "There is enough doubt about what deprenyl might actually do. It might not only be good, but it could actually be bad."

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