Chemistry of Drug Induced Parkinsons

Chemistry Connections

Episode #20

Welcome to Chemistry Connections, my name is Mari Kwak and I am your host for episode #20 called Drug induced Parkinson’s. Today I will be discussing how poorly made “synthetic Heroin” can induce symptoms of Parkinson’s disease in users within one use.

Segment 1: Introduction to Synthetic Heroin and Parkinson’s Disease

Parkinson’s disease is a genetically inherited disorder of the central nervous system, which affects body movement. Over the past 8 or so years, outbreaks of induced parkinson's have been found in California, Maryland, Vancouver, and British Columbia.
This synthetic heroin powder containing MPTP is usually either dissolved in water and injected into the bloodstream or snorted.
Unlike other effects of drugs which take consistent usage over a period of time, this new synthetic drug has caused irreversible symptoms of Parkinson’s within the first use.
Some symptoms of induced Parkinson’s observed in patients are difficulty moving, rigidity, resting tremor, flexed posture, and loss of postural reflexes.
The heroin powder itself, otherwise known as MPPP, does not cause Parkinson's, it's the MPTP that is a byproduct of synthetic heroin that causes Parkinson's-like symptoms.
This background info comes from a CDC article with data from The National Institute on Drug Abuse and the National Institute of Mental Health.

Chemistry time:

The chemical compound N-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine, MPTP, is the accidental byproduct of MPPP, a synthetic opium drug.
MPTP itself is not toxic, but when it oxidizes into MPP+ after it breaks the skin barrier, it becomes toxic.
The MAO-B enzyme contained in astrocytes and serotonergic neurons reacts with MPTP in a redox reaction. MAO-B acts as a catalyst, to help facilitate the oxidation reaction of MPTP. First, MPTP is oxidized, by losing an electron, to become the chemical MPDP+. From there, more MAO-B oxidizes MPDP+ into MPP+, by losing another election. The final product, MPP+, is the toxic chemical found to induce Parkinson's.
Why is MPP+ so toxic, you may be wondering? Well… I personally do not know but science considers
MPP+ is considered toxic because it kills dopamine-producing neurons, which have a high affinity for MPP+. → meaning that MPP+ and dopamine-producing neurons are attracted to each other.
Since they have a high affinity, the dopamine transmitter (DAT) takes MPP+ up to DA neutrons, where MPP+ uses its neurotoxicity to interrupt the complex I respiratory chain. The complex I respiratory chain is responsible for catalysing the electron transfer between coenzymes, which are essential for cells to function normally.
Catalysts, like the complex I respiratory chain, increase the rate of reactions, by lowering the activation energy of the reaction. Since the complex I respiratory chain is interrupted, the electron transfers between two essential coenzymes will happen at too slow a rate for these cells to continue functioning.
When these dopamine-producing neurons cannot function properly, they cause disorders like Parkinson’s
In one autopsy of a drug user, MPTP appears to have destroyed the substantia nigra’s nerve cells located in the center bottom of the brain.
The pathway from the substantia nigra to signal the rest of the brain is made up of dopamine using neurons, which are severely damaged by MPP+.
The substantia nigra controls body movement and control so, the destruction of substantia nigra’s nerve cells from MPP+ causes the patient to lose body control and struggle with body movement.
Defects in this area of the brain are seen in both Parkinson’s patients and drug users who ingested MPTP.
The chemical reaction that destroys nerve cells after MPTP is ingested with synthetic heroin, is responsible for inducing Parkinson's-like symptoms in drug users.

Segment 3: Personal Connections

My old coach was trafficking drugs, including heroin, across the country with her son, and I was always wondering how underground chemists, AKA illegal drug makers, make large batches of drugs without lots of failures. It turns out that they do.

I found it interesting to learn about different byproducts that are accidentally created in the formation of different drugs
It's also interesting that medication/drugs can inadvertently mimic a genetic disorder that has no cure or solution.
Although MPTP is not good, it could help chemists and pharma personal understand Parkinson’s disease better
Potentially lead to a cure or further preventative measures to stop symptoms before they develop.

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