Skip to main content
SpringerLink
Log in

l-Dopa

  • Chapter
Drug Discovery

Abstract

Parkinson’s disease (“shaking palsy,” paralysis agitans) is a disabling disease. Its main clinical features are tremor during rest, rigidity, slowness of movement (bradykinesia, akinesia), and impaired postural and righting reflexes. These abnormalities produce dysarthria, dysphagia, festinant gait, mask-like facies, infrequent blinking, drooling, and seborrhea (Hoehn and Yahr, 1967; Marks, 1974). Parkinson’s disease is one of the most common chronic neurologic diseases of late adulthood, striking in the fifth and sixth decade of life (Calne and Sandier, 1970; Perlik et al., 1980). Life expectancy for the untreated patient is only 5-14 yr after diagnosis. Compared to the general population, the untreated Parkinson patient has a shorter life span and a three-times-higher mortality rate. Untreated Parkinsonians are especially susceptible to bronchopneumonia as a consequence of immobilization and debilitation (Hoehn and Yahr, 1967). As the life expectancy of the general population increases, an increase in the number of Parkinson’s disease cases is to be expected.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Barbeau, A.: Preliminary observations on abnormal catecholamine metabolism in basal ganglia diseases. Neurology 10:446–451, 1960.

    Article  PubMed  CAS  Google Scholar 

  • Barbeau, A.: Dopamine and basal ganglia diseases. Arch. Neurol. 4:109–114, 1961.

    Article  Google Scholar 

  • Barbeau, A.: The use of L-dopa in Parkinson’s disease: A 20 year follow up. Trends Pharm. Sci. 2:297–299, 1981.

    Article  Google Scholar 

  • Barbeau, A., Murphy, G. F., and Sourkes, T. L.: Excretion of dopamine in diseases of basal ganglia. Science 133:1706,1707,1961a.

    Article  PubMed  CAS  Google Scholar 

  • Barbeau, A., Sourkes, T. L., and Murphy, G. F.: Les catecholamines dans lamaladie de Parkinson, in Monoamines et Systèmes Nerveaux Central, pp. 247–262, Symp. de Bel Air, Geneva, Sept., 1961b.

    Google Scholar 

  • Bartholini, G., Burkard, W. P., and Pletscher, A.: Increase of cerebral cate-cholamines caused by 3,4-dihydroxyphenylalanine after inhibition of peripheral decarboxylase. Nature 215:852,853,1967.

    Article  PubMed  CAS  Google Scholar 

  • Bennett, D. R., ed.: AMA Drug Evaluations, 5th Ed., pp. 284,1144, American Medical Association, Chicago, 1983.

    Google Scholar 

  • Bertler, A. and Rosengren, E.: Occurrence and distribution of dopamine in brain and other tissues. Experientia 15:10,11,1959.

    Article  PubMed  CAS  Google Scholar 

  • Bertler, A., Carlsson, A., and Rosengren, E.: Release by reserpine of cate-cholamines from rabbit hearts. Naturwissenschaften 43:521, 1956.

    Article  CAS  Google Scholar 

  • Bianchine, J. R.: Drug therapy of Parkinsonism. N. Engl. J. Med. 295:814–818, 1976.

    Article  PubMed  CAS  Google Scholar 

  • Birkmayer, W. and Hornykiewicz, O.: Der L-3,4-Dioxyphenylalanine (=Dopa)-Effekt bei der Parkinson-Akinese. Wien. Klin. VJochenschr. 45: 787,788,1961.

    Google Scholar 

  • Birkmayer, W. and Mentasti, M.: Weitere experimentelle Untersuchungen über den catecholaminstof fwechsel bei extrapyramidalen erkrankungen (Parkinson-und Chorea Syndrom). Arch. Psychiatrie Nerven Kr. 210:29–35, 1967.

    Article  CAS  Google Scholar 

  • Birkmayer, W. and Riederer, P.: Parkinson’s Disease. Biochemistry, Clinical Pathology, and Treatment, Springer-Verlag, New York, 1983.

    Google Scholar 

  • Blaschko, H.: Metabolism and storage of biogenic amines. Experientia 13: 9–12, 1957.

    Article  PubMed  CAS  Google Scholar 

  • Blaschko, H.: The development of current concepts of catecholamine formation. Pharmacol. Rev. 11:307–316, 1959.

    PubMed  CAS  Google Scholar 

  • Calne, D. B.: Developments in the pharmacology and therapeutics of parkinsonism. Ann. Neurol. 1:111–119, 1977.

    Article  PubMed  CAS  Google Scholar 

  • Calne, D. B. and Sandler, M.: L-dopa and parkinsonism. Nature 226:21–24, 1970.

    Article  PubMed  CAS  Google Scholar 

  • Carlsson, A.: L-Dopa: The pharmacological rationale, in Developments in Treatment for Parkinson’s Disease., G. C. Cotzias and F. H. McDowell, eds., pp. 65–77, Medcom, New York, 1971.

    Google Scholar 

  • Carlsson, A.: Biochemical and pharmacological aspects of parkinsonism. Acta Neurol. Scand. (Supp.) 51: 11–42, 1972.

    CAS  Google Scholar 

  • Carlsson, A. and Hillarp, N. A.: Release of adrenaline from the adrenal medulla of rabbits produced by reserpine. Kgl. Fysiogr. Sallsk. Lund Fork 26: Nr8, 1956.

    Google Scholar 

  • Carlsson, A., Lindqvist, M., and Magnusson, T.: 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists. Nature 180: 1200, 1957b.

    Article  PubMed  CAS  Google Scholar 

  • Carlsson, A., Lindqvist, M., Magnusson, T., and Waldeck, B.: On the presence of 3-hydroxytyramine in brain. Science 127:471, 1958.

    Article  PubMed  CAS  Google Scholar 

  • Carlsson, A., Rosengren, E., Bertler, A., and Nilsson, J.: Effect of reserpine on the metabolism of catecholamines, in Psychotropic Drugs, S. Garattini and V. Ghetti, eds., pp. 363–372, Elsevier, New York, 1957a.

    Google Scholar 

  • Cooper, I. S.: The Neurosurgical Alleviation of Parkinsonism, Charles C. Thomas, Springfield, IL, 1956.

    Google Scholar 

  • Cooper, I. S.: L-Dopa from a neurosurgeon’s point of view, in Developments in Treatment for Parkinson’s Disease, G. C. Cotzias and F. H. McDowell, eds., p. 56, Medcom, New York, 1971.

    Google Scholar 

  • Cotzias, G. C: Levodopa in the treatment of parkinsonism. JAMA 218: 1903–1908, 1971.

    Article  PubMed  CAS  Google Scholar 

  • Cotzias, G. C., Van Woert, M. H., and Schiffer, L. M.: Aromatic amino acids and modification of parkinsonism. N. Engl. J. Med. 276:374–379, 1967.

    Article  PubMed  CAS  Google Scholar 

  • Dikshit, R. K.: The story of rauwolfia. Trends Pharm. I (16): viii–x, 1980.

    Google Scholar 

  • Ehringer, H. and Hornykiewicz, O.: Verteilung von noradrenalin und dopamin (3-hydroxytryramin) im gehirn des menschen und ihr verhalten bei erkrankungen des extrapyramidalen systems. Wien. Klin. Wochen-schr. 38:1236–1239, 1960.

    Article  CAS  Google Scholar 

  • Fehling, C: Treatment of Parkinson’s syndrome with L-dopa. A double blind study. Acta Neurol. Scand. 42:367–372, 1966.

    Article  PubMed  CAS  Google Scholar 

  • Friedhoff, A. J., Hekimian, L., Alpert, M., and Tobach, E.: Dihydroxy-phenylalanine in extrapyramidal disease. JAMA 184: 285,286,1963.

    Article  PubMed  CAS  Google Scholar 

  • Hershey, L. A.: Controversies in the treatment of Parkinson’s disease. Ration. Drug Ther. 19:1–7, 1985.

    PubMed  CAS  Google Scholar 

  • Hoehn, M. M. and Yahr, M. D.: Parkinsonism: Onset, progression and mortality. Neurology 17:(5) 427–442, 1967.

    Article  PubMed  CAS  Google Scholar 

  • Hornykiewicz, O.: Advances in neurochemistry and pharmacology of Parkinson’s disease, in Developments in Treatment for Parkinson’s Disease, G. C. Cotzias and F. H. McDowell, eds., pp. 25–31, Medcom, New York, 1971.

    Google Scholar 

  • Hornykiewicz, O.: Dopamine in the basal ganglia. Br. Med. Bull. 29:172–178, 1973.

    PubMed  CAS  Google Scholar 

  • Hornykiewicz, O.: Historical aspects and frontiers of Parkinson’s disease research, in Parkinson’s Disease. Neurological, Clinical and Related Aspects. F. S. Messiha and A. D. Kenny, eds., pp. 1–8, Plenum, New York, 1977.

    Google Scholar 

  • Lesser, R. P., Fahn, S., Snider, S. R., Cote, L. J., Isgreen, W. P., and Barrett, R. E.: Analysis of the clinical problems in parkinsonism and the complications of long-term levodopa therapy. Neurology 29:1253–1260, 1979.

    Article  PubMed  CAS  Google Scholar 

  • Lieberman, A., Neophytides, A., Kupersmith, M., Casson, I., Durso, R., Hoo Foo, S., Khayali, M., Tartaro, T., and Goldstein, M.: Treatment of Parkinson’s disease with dopamine agonists: A review. Am. J. Med. Sci. 278: 65–76, 1979.

    Article  PubMed  CAS  Google Scholar 

  • Lloyd, K. and Hornykiewicz, O.: Parkinson’s Disease: Activity of L-dopa decarboxylase in discrete brain regions. Science 170:1212,1213,1970.

    Article  PubMed  CAS  Google Scholar 

  • McDowell, F. H.: Developments in Treatment for Parkinson’s Disease, G. C. Cotzias and F. H. McDowell, eds., p. 9, Medcom, New York, 1971.

    Google Scholar 

  • McGeer, P. L., Boulding, J. E., Gibson, W. C., and Foulkes, R. G.: Drug-induced extrapyramidal reactions. JAMA 177:665–670, 1961.

    Article  PubMed  CAS  Google Scholar 

  • McGeer, P. L. and Zeldowicz, L. R.: Administration of dihydroxyphenyl-alanine to parkinsonian patients. J. Can. Med. Assoc. 90:463–466, 1964.

    CAS  Google Scholar 

  • Marks, J.: Trials of oral therapy, in The Treatment ofParkinsonism with i-Dopa, pp. 81–83, American Elsevier, New York, 1974.

    Google Scholar 

  • Müller, J. M., Schüttler, E., and Bein, H. J.: Reserpin, der sedative Wirkstoff aus Rauwolfia serpentina Benth. Experientia 8:338, 1952.

    Article  PubMed  Google Scholar 

  • Perlik, S. J., Koller, W. C., Weiner, W. J., Nausieda, P., and Klawans, H. L.: Parkinsonism: Is your treatment appropriate? Geriatrics 35: (II) 65–74, 1980.

    PubMed  CAS  Google Scholar 

  • Pletscher, A., Shore, P. A., and Brodie, B. B: Serotonin as a mediator of re-serpine action in brain. J. Pharmacol. Exp. Ther. 116:84–89, 1956.

    PubMed  CAS  Google Scholar 

  • Raab, W.: Specific sympathomimetic substance in the brain. Am.J.Physiol. 152:324–339, 1948.

    PubMed  CAS  Google Scholar 

  • Raab, W. and Gigee, W.: Concentration and distribution of “encephalin“ in the brain of humans and animals. Proc. Soc. Exp. Biol. Med. 76:97–100, 1951.

    PubMed  CAS  Google Scholar 

  • Sano, I., Gamo, T., Kakimoto, Y., Taniguchi, K., Takesada, M., and Nishi-numa, K.: Distribution of catechol compounds in human brain. Biochim. Biophys. Ada 32:586,587,1959.

    Article  CAS  Google Scholar 

  • Shaw, K. M., Lees, A. J., and Stern, G. M.: The impact of treatment with levo-dopa on Parkinson’s disease.Q. J. Med. 195:283–293, 1980.

    Google Scholar 

  • Steck, H. Le syndrome extra-pyramidal et diencéphalique au cours des traitements au Largactil et au Serpasil. Ann. Méd. Psychol. (Paris) 112(2):737–743, 1954.

    CAS  Google Scholar 

  • Udenfriend, S., Zaltzman-Nirenberg, P., Gordon, R., and Spector, S.: Evaluation of the biochemical effects produced in vivo by inhibitors of the three enzymes involved in norepinephrine biosynthesis. Mol. Pharmacol. 2:95–105, 1966.

    PubMed  CAS  Google Scholar 

  • Woodruff, G.N.: Dwindlingdopaminereceptors. Trends Pharm.Sci. 7:252, 253,1986.

    Article  Google Scholar 

  • Yahr, M. D.: Levodopa. Ann. Intern. Med. 83:677–682, 1975.

    PubMed  CAS  Google Scholar 

  • Yahr, M. D.: Overview of present day treatment of Parkinson’s disease. J. Neural Transm. 43:227–238, 1978.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Wellcome Research Laboratories Research, Triangle Park, North Carolina, USA

    Robert A. Maxwell

  2. University of Vermont College of Medicine, Burlington, Vermont, USA

    Shohreh B. Eckhardt

Authors
  1. Robert A. Maxwell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shohreh B. Eckhardt
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 1990 Springer Science+Business Media New York

About this chapter

Cite this chapter

Maxwell, R.A., Eckhardt, S.B. (1990). l-Dopa. In: Drug Discovery. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4612-0469-5_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-4612-0469-5_14

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4612-6775-1

  • Online ISBN: 978-1-4612-0469-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation