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

  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},
  volume={219 4587},
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… 

MPTP-Induced Parkinsonian Syndromes in Humans and Animals

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.

Permanent human parkinsonism due to 1‐methy 1–4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)

Neither prolonged levodopa treatment nor progressive disease was necessary for on-off phenomena, because the neurotoxic effects of MPTP seem limited to the substantia nigra, and damage to this system alone may produce all the motor features of Parkinson's disease.

Experimental parkinsonian syndrome induced in rats by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

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.

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.

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

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.




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.