Parkinson's disease: Past, present, and future

Abstract

Development of understanding of the pathophysiology II modes of treatment of Parkinson's disease represents of the triumphs of modern medicine, encompassing estute clinical observation, utilization of basic research fasdings regarding dopamine to develop the first rational treatment of a degenerative disorder of the central ItIroUs system, and remains at the frontiers of neurology science. After characterization of the clinical II pathologic features of Parkinson's disease, rational treatment awaited the discovery of the deficit in basal penglia dopamine. On the basis of this observation and known biosynthetic pathways for dopamine famation, levodopa was introduced. Use of metabolic chubitors to prolong and potentiate the effects and avoid the deleterious side effects of levodopa enhanced the of this neurotransmitter replacement strategy. the discovery and characterization of dopamine receptor and the availability of selective dopamine qeonisfs provided additional therapeutic approaches, but fold to address the underlying cause of the degenerative process. The discovery and disclosure of the mechanisms of toxicity of the relatively selective nigrostriatal neurotoxin, l-methyl-4-phenyl-l, 2, 5, 6-tetrahydropyridine (MPTP), triggered a resurgence of interest in etiological factors which might contribute to the development of parkinsonism and together with the report that inhibition of monoamine oxidase B with deprenyl not only potentiated the effects of levodopa, but appeared to prolong the life of parkinsonian patients, resulted in a large-scale trial of drugs that might arrest the degenerative process. Furthermore, the MPTP primate model of Parkinson's disease has encouraged development of fetal mesencephalic and other tissue implant approaches to reversal of parkinsonism. Although much of this is still in the experimental stages, hopes are high that new and more effective therapies will be developed and that similar techniques might be applicable to a wide variety of neuropsychiatric disorders. © 1993, American College of Neuropsychopharmacology. All rights reserved.