Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis.

@article{Langston1983ChronicPI,
  title={Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis.},
  author={James W. Langston and Phillip Ballard and James W. Tetrud and Ian Irwin},
  journal={Science},
  year={1983},
  volume={219 4587},
  pages={
          979-80
        }
}
Four persons developed marked parkinsonism after using an illicit drug intravenously. Analysis of the substance injected by two of these patients revealed primarily 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) with trace amounts of 1-methyl-4-phenyl-4-propionoxy-piperidine (MPPP). On the basis of the striking parkinsonian features observed in our patients, and additional pathological data from one previously reported case, it is proposed that this chemical selectively damages cells in… 
View on PubMed
doi.org
4,695 Citations
Highly Influential Citations
139
Background Citations
1,304
Methods Citations
61
Results Citations
30

4,695 Citations

MPTP-Induced Parkinsonian Syndromes in Humans and Animals
TLDR
The history of this discovery, the present knowledge of MPTP- induced motor disorders, and the implications for understanding spontaneously occurring Parkinson’s Disease are recounted.
MPTP-induced parkinsonism in monkeys: mechanism of action, selectivity and pathophysiology.
  • W. Schultz
  • Biology, Medicine
    General pharmacology
  • 1988
Experimental parkinsonian syndrome induced in rats by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
TLDR
The basic pathogenetic mechanism of the parkinsonian syndrome arising under the influence of MPTP is associated with degeneration of the dopaminergic neurons of the substantia nigra, as a result of which a dopamine deficiency develops in the caudate nuclei (CN).
Pattern of dopaminergic loss in the striatum of humans with parkinsonism induced by MPTP.
TLDR
It transpired that the chemist who had made the offending drug had unwittingly synthesised 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which proved to be a potent and specific nigral toxin.
A sheep model for MPTP induced Parkinson-like symptoms.
Detection of Tetrahydroisoquinoline, a Parkinsonism-Related Compound, in Parkinsonian Brains and Foods by Gas Chromatography-Mass Spectrometry
After 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was discovered to cause parkinsonism in humans, monkeys, and mice,1–2 Nagatsu et al. screened various compounds structurally similar to MPTP…
Clinical and biochemical parameters of parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and its methyl-phenyl and methoxy-phenyl derivatives in C57B1/6 mice
TLDR
Only Ortho-methylphenyl- and ortho-methoxyphenyl-derivates of MPTP cause a persistent loss in dopamine content in the brain and produced the clinical symptoms of parkinsonism.
An endogenous substance of the brain, tetrahydroisoquinoline, produces parkinsonism in primates with decreased dopamine, tyrosine hydroxylase and biopterin in the nigrostriatal regions
A parkinson-like neurologic deficit in primates is caused by a novel 4-substituted piperidine
Monoamine Oxidase-A and -B and the Bioactivation of MPTP-like Neurotoxins
TLDR
The clinical features observed in the affected individuals include tremor, rigidity and akinesia, the three symptoms ordinarily seen in the Parkinsonian patient.
...
...

References

SHOWING 1-3 OF 3 REFERENCES
Chronic parkinsonism secondary to intravenous injection of meperidine analogues
APRAXIA OF LID OPENING.
Apraxia of lid opening is a nonparalytic motor abnormality characterized by the patient's difficulty in initiating the act of lid elevation. It differs from paralytic ptosis by being present only…
Piperidine derivatives; 4-arylpiperidines.