Parkinsonism Induced By 1-Methyl-4-Phenyl-1, 2, 3, 6-Tetrahydropyridine (MPTP): Implications for Treatment and the Pathogenesis of Parkinson’s Disease

ABSTRACT Our experience in treating 7 patients with moderate to severe parkinsonism induced by l-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) is reviewed. Virtually all of the problems typically encountered with dopamine precursor and agonist therapy in treating Parkinson’s disease have been observed during a one and one half year follow-up period, including “end-of-dose” deterioration (or “wearing off’), “peak-dose” dyskinesias, “on-off” phenomena, and psychiatric complications. These have occurred much earlier than is typically seen when treating the idiopathic disease. This rapid evolution of therapeutic side-effects favors the view that at least some of the complications of dopamine precursor therapy may be related to severity of disease rather than the length of levodopa therapy. Finally, we suggest that the occurrence of this full array of therapeutic complications in patients with MPTP-induced parkinsonism furthers the analogy between this syndrome and Parkinson’s disease.

[1]  W. Weiner,et al.  Levodopa‐Induced dopamine receptor hypersensitivity , 1977, Transactions of the American Neurological Association.

[2]  G. Siegel,et al.  Analysis of l-dopa induced dyskinesias in 51 patients with Parkinsonism , 1971, Journal of neurology, neurosurgery, and psychiatry.

[3]  Sanford P. Markey,et al.  Chronic parkinsonism secondary to intravenous injection of meperidine analogues , 1979, Psychiatry Research.

[4]  J. Langston,et al.  Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. , 1983, Science.

[5]  R P Lesser,et al.  Analysis of the clinical problems in parkinsonism and the complications of long‐term levodopa therapy , 1979, Neurology.

[6]  D. Jacobowitz,et al.  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. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[7]  C. Rebert,et al.  Selective nigral toxicity after systemic administration of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyrine (MPTP) in the squirrel monkey , 1984, Brain Research.

[8]  A. Friedhoff,et al.  Reversal of two manifestations of dopamine receptor supersensitivity by administration of L-dopa. , 1977, Research communications in chemical pathology and pharmacology.

[9]  S. Fahn.  Fluctuations of disability in Parkinson's disease: pathophysiology , 1981 .

[10]  C. Marsden,et al.  Early onset of the "on-off" phenomenon in children with symptomatic Parkinsonism. , 1982, Journal of neurology, neurosurgery, and psychiatry.

[11]  M. Muenter,et al.  L-dopa therapy of Parkinson's disease: plasma L-dopa concentration, therapeutic response, and side effects. , 1971, Mayo Clinic proceedings.

[12]  P. Seeman,et al.  L-DOPA reversal of hyperdopaminergic behaviour. , 1978, Life sciences.

[13]  Mones Rj,et al.  Analysis of l-dopa induced dyskinesias in 51 patients with Parkinsonism , 1971 .

[14]  J. D. Parkes,et al.  "ON-OFF" EFFECTS IN PATIENTS WITH PARKINSON'S DISEASE ON CHRONIC LEVODOPA THERAPY , 1976, The Lancet.

[15]  M. Hoehn,et al.  Parkinsonism , 1967, Neurology.

[16]  A. Granérus.  Factors influencing the occurrence of "on-off" symptoms during long-term treatment with L-dopa. , 2009, Acta medica Scandinavica.

[17]  F. Mcdowell,et al.  Five years' treatment of Parkinson's disease with levodopa. Therapeutic results and survival of 100 patients. , 1975, Annals of internal medicine.