Friday, February 1, 2013

Thank You Heroin Addicts!

Greg Parker

"George Castillo knew something was wrong the moment he injected the heroin.  His arm burned as if hot lead were flowing into his veins, giving him a stunning high, the best he had had for years.  Then he began to hallucinate strangely, trying to walk through doors that weren't there, hurting himself each time he plowed into a wall.  George vaguely wondered about those four bindles he had bought on the street in Mountain View, but then he fell into an uncomfortable sleep.  The next morning George awoke feeling as if his body had turned to stone."   -The Case of the Frozen Addicts

The 1970's were rough times for heroin addicts and dealers in the United States.  Heroin was in short supply due to conflicts in Afghanistan and Turkey, so drug users looked for other sources of intoxication, but it was hard to match the powerful analgesic effect of the natural poppy plant.  Users started to use such synthetic opiates such as morphine, fentanyl, meperidine (demerol), buprenorphine, and codeine.  Soon, bright young capitalists attempted to fill this demand, and began to produce "designer drugs".  The idea was: why try to buy and distribute illegal drugs when they could make new drugs that give a similar high, but are not  illegal? 

One of the new drugs that these young chemists focused on was a fentanyl analog, called 1-methyl-4-phenyl-propionoxy-piperdine (MPPP), synthesized from a few ordinary industrial chemicals.  This analog was so potent that very small amounts had to be synthesized.  The finished product was 99.99 percent filler and 0.01 percent synthesized opiate, turning $10,000 into $1 million easier than Steve Jobs.  

One of these junior chemists was named Barry Kidston.  He was armed with the writings of the original MPPP synthesizer and La Roche chemist, Dr. Albert Ziering and a home chemistry set.  Following Dr. Ziering's formula, Barry began to produce, use, and sell MPPP during the summer of 1976.  All this came to an end abruptly in November, when Barry rushed a batch.  He injected into his arm, and knew something was wrong.  Within three days he was frozen, unable to speak or walk.  He was taken to the hospital by his parents, misdiagnosed with catatonic schizophrenia, and treated with electroconvulsive therapy for months.  Finally, a neurologist was called in and diagnosed him with Parkinson's disease.  The L-dopa treatment unfroze him almost immediately.  Soon after, researchers analyzed the hurried dope, and concluded that it was comprised of both MPPP and a similar compound, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a previously unknown molecule.  Barry died of cocaine overdose shortly after treatment began.

Parkinson's disease is due to damage of dopaminergic neurons in the substantia nigra, shutting down dopamine production, and limiting movement substantially.  There are some treatments, like MAO-B inhibitors and L-dopa, but there effects wear off over time, leaving a poor prognosis for Parkinson's patients.  

Shortly after the hospitalization of Barry, six other patients presented with identical symptoms.  They too were misdiagnosed and mistreated.  It soon became clear that all seven of these drug users had used MPTP, which had damaged the dopaminergic neurons, seen only in Parkinson's patients.  This fact, although sad for those seven, was seen as a breakthrough in the research community.  Until then, there hadn't been a Parkinson's model for researchers to test treatments on.  Researchers and neurologists jumped at this opportunity to create a new disease model.  Dr. Bill Langston was one of the first medical doctors to begin using the MPTP model, and the MPTP model is still used today.  There are currently four synthetic molecules used to create the Parkinson's disease model: 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, and paraquat.

Thank you heroin addicts!

Five of the six "frozen addicts", Fall 1991.  

Dr. Bill Langston

Langston, W.J., and J. Palfreman. 1995. The Case of the Frozen Addicts. New York, NY: Random House.

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