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Chronic Parkinsonism in Humans Due to a Product of Meperidine-Analog Synthesis
Abstract
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 the substantia nigra.
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“The most compelling evidence of mitochondrial dysfunction in PD comes from the accidental discovery of the synthetic meperidine analogue 1-methyl-4-phenyl-1,2,3,6-tetrahydrodropyridine (MPTP), which causes parkinsonism by selective inhibition of mitochondrial complex-I of the electron transport chain4, 5.”
From Mitochondrial Approaches for Neuroprotection (2008) · cites this paper as [4]
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Shang, T., Kotamraju, S., Kalivendi, S. V., Hillard, C. J., & Kalyanaraman, B. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m400101200 · Cited by 62
Metadata
- Authors
- Langston, J. W., Ballard, P., Tetrud, J. W., & Irwin, I.
- ORCID
- Ballard, Philip
- Venue
- Science
- Published
- 1983-02-25
- Volume
- 219
- Issue
- 4587
- Pages
- 979-980
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1969800514
- Cited by
- 4,914
- References
- 3
- Citations by year
- 2026: 54 · 2025: 73 · 2024: 88 · 2023: 105 · 2022: 120 · 2021: 126 · 2020: 156 · 2019: 116 · 2018: 135 · 2017: 149 · 2016: 104 · 2015: 121 · 2014: 131 · 2013: 146 · 2012: 151
- FWCI
- 122.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Keywords
- parkinsonism, MPTP, intravenous drug use, substantia nigra, neurotoxicity, Parkinson's disease
- MeSH terms
- Adult, Female, Humans, Male, Meperidine, Opioid-Related Disorders, Parkinson Disease, Secondary, Substantia Nigra
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