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Aim high: synthetic opiates deliver surprising side effects.

Barry Kidston didn't think that studying chemistry was enough of a high. So in 1976, the University of Maryland graduate student filled a syringe with a drug he synthesized, and eager for euphoria, plunged it into his arm. Kidston had apparently come across a paper written in 1947 by Albert Ziering, a researcher at the Hoffmann-La Roche pharmaceutical company, who had been working on synthetic narcotics with a view towards developing pain killers that were less addictive than morphine. Ziering had examined compounds that were variants of Demerol, a synthetic opiate already in use. By making a subtle change in the structure of the molecule, he had hoped to come up with an improved drug. But it seems the novel substance, 1-methyl-4-phenyl-4-propionoxy-piperidine (MPPP) was no better than Demerol, and it was never marketed. Kidston knew that making a controlled substance such as Demerol was illegal. If caught, he would trade in his lab coat for prison garb. But MPPP was a different story. Since it had never been introduced into the marketplace, it was not a controlled substance. And for someone with a background in chemistry, it wasn't hard to make.

At first, the results were just as expected. Kidston was overcome with the type of exhilaration normally associated with opiates. He continued to inject himself with the drug over a period of several months. Whenever be needed more, he just brewed up another batch in the lab. Then one day the fun came to an abrupt halt. After injecting himself, he noticed a burning sensation followed by some terrifying symptoms. All of a sudden, his limbs felt leaden. Within three days, he could hardly more. Kidston was hospitalized, but the doctors were perplexed. "Catatonic schizophrenia" was bandied about, but the drugs prescribed only made him worse. A neurologist suggested that the symptoms looked like Parkinson's disease, although this would have been a real rarity in someone so young. Ata loss, the doctors tried treatment with L-Dopa, the classic Parkinson's medication. It worked!

L-Dopa enters the brain where it is converted into dopamine, the neurotransmitter that is in short supply in Parkinson's disease. Somehow, Kidston's synthetic drug had destroyed the brain cells that produce dopamine. One would think such a disastrous experience would end any quest for a chemical high, but no. Two years later, Barry Kidston died of a cocaine overdose. An autopsy revealed a substantial loss of dopamine-producing cells in the substantia nigra part of his brain, a hallmark of Parkinson's disease. But why had he been happily high for months before being brought down by a new batch of the drug? Investigators were stumped, but found the case was interesting enough to merit publication. Several major journals rejected the paper, saying that it was only a single case report, but eventually it was accepted for publication in Psychiatry Research, where it lay buried until 1982.

That's when George Carrillo, a 42-year-old drug addict, showed up in a hospital emergency room, barely able to walk or talk. His hand trembled as he tried to explain that the symptoms appeared soon after he injected himself with some "new heroin," purchased on the street. A week later, his girlfriend appeared, similarly afflicted. Doctors William Langston and Philip Ballard, the attending neurologists, were mystified. This looked like Parkinson's disease, but they had never seen it present in this fashion. Parkinson's is extremely rare in people under 50 and does not come on all of a sudden! Could this be some sort of novel variant induced by the "new heroin?"

Dr. Ballard heard about a third young heroin addict who had mysteriously "turned to stone." This was enough to issue a public warning about potentially tainted heroin, a warning that brought three more cases to light. A sample of the "new heroin" was sent for analysis, and one of the toxicologists who received a sample along with the accompanying case report recalled reading about an unusual case of Parkinson's in Psychiatry Research. When Dr. Langston heard this, he looked up the paper and saw the reference to Ziering's original account.

A quick trip to the Stanford University library turned up the 1947 volume of The Journal of Organic Chemistry, but Langston was shocked to see that Ziering's paper had been cut out! It was clear now that some enterprising chemist was cooking up MPPP and selling it as "new heroin." But MPPP had undergone drug testing and had never been connected with Parkinson's disease. As Langston pursued the chemistry of MPPP, he came across something interesting. Apparently, if Ziering's original synthesis was not followed exactly, a contaminant, called MPTP, was produced. When MPTP was injected into monkeys, it triggered the symptoms of Parkinson's disease!

Now the mist cleared. Both Kidston and the clandestine California chemist had done some sloppy work and produced batches of MPPP that were contaminated with a Parkinson's causing chemical. But they also may have cast light on the causes of Parkinson's disease and perhaps explained why the disease is more prevalent in agricultural areas. MPTP has a striking chemical similarity to some pesticides! The cloud that hangs over Barry Kidston's misuse of chemistry may yet turn out to have a silver lining.

Popular science writer, Joe Schwarcz, MCIC, is a chemistry professor and the director of McGill University's Office for Science and Society. He hosts the Dr. Joe Show every Sunday from 3:00 to 4:00 p.m. on Montreal's radio station CJAD and on CFRB in Toronto. The broadcast is available on the Web at www.CJAD.com.
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Title Annotation:CHEM FUSION
Comment:Aim high: synthetic opiates deliver surprising side effects.(CHEM FUSION)
Author:Schwarz, Joe
Publication:Canadian Chemical News
Geographic Code:1CANA
Date:Nov 1, 2005
Words:922
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