• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Jul 1983; 80(14): 4546–4550.
PMCID: PMC384076

A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.


A syndrome similar to idiopathic parkinsonism developed after intravenous self-administration of an illicit drug preparation in which N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NMPTP) might have been responsible for the toxicity. In the present study we show that intravenous administration of NMPTP to the rhesus monkey produces a disorder like parkinsonism (akinesia, rigidity, postural tremor, flexed posture, eyelid closure, drooling) that is reversed by the administration of L-dopa. NMPTP treatment decreases the release of dopamine and dopamine accumulates in swollen, distorted axons in the nigrostriatal pathway just above the substantia nigra, followed by severe nerve cell loss in the pars compacta of the substantia nigra and a marked reduction in the dopamine content of the striatum. The pathological and biochemical changes produced by NMPTP are similar to the well-established changes in patients with parkinsonism. Thus, the NMPTP-treated monkey provides a model that can be used to examine mechanisms and explore therapies of parkinsonism.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.7M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Cotzias GC, Van Woert MH, Schiffer LM. Aromatic amino acids and modification of parkinsonism. N Engl J Med. 1967 Feb 16;276(7):374–379. [PubMed]
  • Parkes JD, Marsden CD, Donaldson I, Galea-Debono A, Walters J, Kennedy G, Asselman P. Bromocriptine treatment in Parkinson's disease. J Neurol Neurosurg Psychiatry. 1976 Feb;39(2):184–193. [PMC free article] [PubMed]
  • Davis GC, Williams AC, Markey SP, Ebert MH, Caine ED, Reichert CM, Kopin IJ. Chronic Parkinsonism secondary to intravenous injection of meperidine analogues. Psychiatry Res. 1979 Dec;1(3):249–254. [PubMed]
  • Langston JW, Ballard P, Tetrud JW, Irwin I. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science. 1983 Feb 25;219(4587):979–980. [PubMed]
  • Jenden DJ, Roch M, Booth RA. Simultaneous measurement of endogenous and deuterium-labeled tracer variants of choline and acetylcholine in subpicomole quantities by gas chromatography-mass spectrometry. Anal Biochem. 1973 Oct;55(2):438–448. [PubMed]
  • Gordon EK, Oliver J, Black K, Kopin IJ. Simultaneous assay by mass fragmentography of vanillyl mandelic acid, homovanillic acid, and 3-methoxy-4-hydroxy-phenethylene glycol in cerebrospinal fluid and urine. Biochem Med. 1974 Sep;11(1):32–40. [PubMed]
  • LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed]
  • Jimerson DC, Markey SP, Oliver JA, Kopin IJ. Simultaneous measurement of plasma 4-hydroxy-3-methoxyphenylethylene glycol and 3,4-dihydroxyphenylethylene glycol by gas chromatography mass spectrometry. Biomed Mass Spectrom. 1981 Jun;8(6):256–259. [PubMed]
  • Colburn TR, Smith BM, Guarini JJ, Simmons NN. An ambulatory activity monitor with solid state memory. ISA Trans. 1976;15(2):149–154. [PubMed]
  • Finch CE. Catecholamine metabolism in the brains of ageing male mice. Brain Res. 1973 Mar 30;52:261–276. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...