What is 1 methyl 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

A chemical derivative of the illicit narcotic known as MPPP, pethidine or MPP+ (chemically, 1-methyl-4-phenyl-4-propionoxypiperidine). When this synthetic heroin breaks down in the body, one of the substances it forms is the toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, known as MPTP, which interferes with the action of mitochondrial enzyme complex i. This interference causes cells to die. In the 1980s MPPP became briefly popular as a “designer drug” to enhance or substitute for heroin among addicts, until its dangers became clear. Many who used it experienced rapid and severe onset of Parkinson’s symptoms, which researchers finally were able to conclude were the result of exposure to MPTP as accidental by-product of attempting to synthesize MPPP. Researchers exploring the connection discovered, by injecting MPTP into laboratory monkeys, that

MPTP creates lesions in the substantia nigra that prevent dopaminE production in a replication of the pathological course of Parkinson’s disease. This was the first time that scientists were able to reproduce Parkinson’s disease in laboratory animals, opening the door to new directions in research.

Because MPTP is a common ingredient in many pesticides currently used for outdoor application throughout the United States, speculation about a possible correlation between idiopathic Parkinson’s disease and long-term, low-level exposure to such chemicals in the environment has led to research studies about their potential association. Although initial findings appeared promising, extended studies have not been conclusive. Exposure to environmental toxins remains one of several theorized causes of Parkinson’s disease. Researchers continue to study MPTP-induced parkinsonism to explore new treatments as well as to gain better understanding of the on-off state and wearing-off state that are typical of the mainstay of drug treatment for Parkinson’s disease, levodopa.

Although MPTP-induced Parkinson’s disease in the laboratory offers scientists the best understanding yet of the mechanisms and pathological process of Parkinson’s disease, MPTP-induced parkinsonism differs in several key ways from the idiopathic form of the disease that most commonly afflicts humans. MPTP-induced parkinsonism symptoms appear rapidly and severely, sometimes within just a few days, in addicts injecting MPTP-contaminated drugs. Damage occurs only in the substantia nigra, and lewy bodies are not present. Also, unlike most other drug-induced parkinsonisms, MPTP-induced parkinsonism is permanent and often quickly fatal.