Skip to main content
Log in

The pharmacology of Parkinson's disease: Basic aspects and recent advances

  • Reviews
  • Published:
Experientia Aims and scope Submit manuscript

Summary

Basic aspects and recent advances in the understanding of the pharmacological mechanism of action of the clinically most used antiparkinson drugs are reviewed. Recent human and animal biochemical investigations clearly confirm and extend previous findings indicating that benserazide is much more potent than carbidopa as peripheral decarboxylase inhibitor. L-DOPA in combination with benserazide or carbidopa constitutes the best available therapy for Parkinson's disease (PD). To reduce peaks and rapid fluctuations of L-DOPA plasma levels (possibly responsible for peak-dose dyskinesias and end-of-dose deterioration) a slow-release formulation of L-DOPA in combination with benserazide or with benserazide plus catechol-O-methyltransferase inhibitors should be developed. In parkinsonian patients under long-term L-DOPA therapy monoamine oxidase inhibitors type B (MAO-B) e.g. (−)-deprenyl and firect dopamine receptor agonists (bromocriptine, lisuride, pergolide etc.), due to their L-DOPA-sparing effects, alleviate in some cases L-DOPA-induced side-effects e.g. dyskinesias and on-off phenomena. However, since (−)-deprenylm, due to its metabolism to (−)methamphetamine and (−)amphetamine, seem to have indirect sympathomimetic activity, new selective MAO-B inhibitors devoid of indirect sympathomimetic effects should be tested clinically to assess the functional role of pure MAO-B inhibition in the therapy of PD. The auxiliary therapy with direct dopmaine receptor agonists of the D-2 subtype represents another valid approach which should be further investigated in order to find novel dopamine agonists, less expensive than bromocriptine and strictly selective for D-2 receptor sites.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Andén, N.E., and Grabowska, M., Pharmacological evidence for a stimulation of dopamine neurons by noradrenaline neurons in brain. Eur. J. Pharmac.39 (1976) 275–282.

    Article  Google Scholar 

  2. Barbeau, A., Murphy, G.F., and Sourkes, T.L., Excretion of dopamine in diseases of basal ganglia. Science133 (1961) 1706.

    Article  CAS  PubMed  Google Scholar 

  3. Barbeau, A., L-DOPA therapy in Parkinson's disease. A critical review of nine years experience. Can. med. Ass. J.101 (1969) 58–89.

    Google Scholar 

  4. Barbeau, A., The clinical physiology of side effects in long-term L-DOPA therapy. Adv. Neurol.5 (1974) 347–365.

    CAS  PubMed  Google Scholar 

  5. Barbeau, A., and Ry, M, Six-year results of treatment with levodopa plus benserazide in Parkinson's disease. Neurology (Minneap.)26 (1976) 399–404.

    Article  CAS  Google Scholar 

  6. Bartholini, G., Burkard, W.P., Pletscher, A., and Bates, H.M., Increase of cerebral catecholamines caused by 3,4-dihydroxyphenylalanine after inhibition of peripheral decarboxylase. Nature215 (1967) 852–853.

    Article  CAS  PubMed  Google Scholar 

  7. Bartholini, G., and Pletscher, A., Effect of various decarboxylase inhibitors on the cerebral metabolism of dihydroxyphenylaline. J. Pharm. Pharmac.21 (1969) 323–324.

    Article  CAS  Google Scholar 

  8. Bartholini, G., and Pletscher, A., Decarboxylase inhibitors. Pharmac. Thera. B1 (1975) 407–421.

    CAS  Google Scholar 

  9. Birkmayer, W., Long-term treatment with L-deprenyl. J. neural. Transm.43 (1978) 239–244.

    Article  CAS  PubMed  Google Scholar 

  10. Birkmayer, W., Danielczyk, W., and Riederer, P., Symptoms and side effects in the course of Parkinson's disease. J. nrural Transm., suppl.19 (1983) 185–199.

    Google Scholar 

  11. Birkmayer, W., and Hornykiewicz, O., Der L-Dihydroxy-phenylalanin (L-DOPA)-Effekt bei Parkinson-Akinesie. Wien. klin. Wschr.73 (1961) 787.

    CAS  PubMed  Google Scholar 

  12. Birkmayer, W., Linauer, W., and Mentasti, M., Traitement à la L-Dopa combinée avec un inhibiteur de la décarboxylase (Ro 4-4602), in Monoamines, Noyaux gris centraux et syndrome de Parkinson, pp 435–441. Eds J. de Ajuriaguerra and G. Gauthier Symposium Bel-Air IV. Georg & Cie, Genève 1971.

    Google Scholar 

  13. Birkmayer, W., and Mentasti, M., Weitere experimentelle Untersuchungen über den Katecholaminstoffwechsel bei extrapyramidalen Erkrankungen (Parkinson- und Chorea-Syndrom). Arch. Psychiat. NervKrankh.210 (1967) 29–35.

    Article  CAS  Google Scholar 

  14. Birkmayer, W., Riederer, P., Linauer, W., and Knoll, J., L-Deprenyl plus L-phenyalanine in the treatment of depression. J. neural Transm.59 (1984) 81–87.

    Article  CAS  PubMed  Google Scholar 

  15. Birkmayer, W., Riederer, P., Ambrosi, L., and Youdim, M.B.H., Implications of combined treatment with Madopar and L-deprenyl in Parkinson's disease. Lancet1 (1977) 59–63.

    Google Scholar 

  16. Birkmayer, W., Riederer, P., Youdim, M.B.H., and Linauer, W., The potentiation of the anti-akinetic effect after L-Dopa treatment by an IMAO-B, deprenyl. J. neural Transm.36 (1975) 303–326.

    Article  CAS  PubMed  Google Scholar 

  17. Burkard, W.P., Gey, K.F., and Pletscher, A., Inhibition of decarboxylase of aromatic aminoacids by 2, 3, 4-trihydroxybenzylhydrazine and its seryl derivative. Archs Biochem.107 (1964) 187–196.

    Article  CAS  Google Scholar 

  18. Buu, N.T., Kuchel, O., and Parent, M.T., Competitive inhibition of catechol-O-methyltransferase by Ro 4-4602. Can. J. Biochem.55 (1977) 771–773.

    Article  CAS  PubMed  Google Scholar 

  19. Calne, D.B., Reid, J.L., and Vakil, S.D., Idiopathic parkinsonism treated with an extracerebral decarboxylase inhibitor in combination with levodopa. Br. med. J.3 (1971) 729–732.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Calne, D.B., Williams, A.C., Neophytides, A., Plotkin, C., Nutt, J.G., and Teychenne, P.F., Long-term treatment of Parkinsonism with bromocriptine. Lancet1 (1978) 735–738.

    Article  CAS  PubMed  Google Scholar 

  21. Calne, D.B., Clinical relevance of dopamine receptor classification. Trends Pharmac. Sci.3 (1980) 412–414.

    Article  Google Scholar 

  22. Cohen, G., The pathobiology of Parkinson's disease: biochemical aspects of dopamine neuron senescence. J. neural Transm., suppl.19 (1983) 89–103.

    Google Scholar 

  23. Corrodi, H., Fuxe, K., Hökfelt, T., Lidbrink, P., and Ungerstedt, U., Effects of ergot drugs on central catecholamine neurons: evidence for a stimulation of central dopamine neurons. J. Pharm. Pharmac.25 (1973) 409–412.

    Article  CAS  Google Scholar 

  24. Corrodi, H., Farnebo, L.O., Fuxe, K., and Hamberger, B., Effect of ergot drugs on central 5-hydroxytryptamine neurons: evidence for 5-hydroxytryptamine release or 5-hydroxytryptamine receptor stimulation. Eur. J. Pharmac.30 (1975) 172–181.

    Article  CAS  Google Scholar 

  25. Cotzias, G.C., van Voert, M.H., and Schiffer, L.M., Aromatic aminoacids and modification of Parkinsonism. N. Engl. J. Med.276 (1967) 374.

    Article  CAS  PubMed  Google Scholar 

  26. Cotzias, G.C., Papavasiliou, P.S., and Gelline, R., Modification of Parkinsonism: chronic treatment with L-DOPA. N. Engl. J. Med.280 (1969) 337–345.

    Article  CAS  PubMed  Google Scholar 

  27. Creese, I., Dopamine receptors explained. Trends Neurosci.5 (1982) 40–43.

    Article  CAS  Google Scholar 

  28. Csanda, E., Antal, J., Antony, M., and Csanaky, A., Experiences with L-deprenyl in Parkinsonism. J. neural Transm.43 (1978) 263–269.

    Article  CAS  PubMed  Google Scholar 

  29. Csanda, E., Tárczy, M., Takáts, A., Mogyrós, I., Köves, A., and Katona, G., L-Deprenyl in the treatment of Parkinson's disease. J. neural Transm., suppl. 19 (1983) 283–290.

    Google Scholar 

  30. Da Prada, M., and Zürcher, G., Simultaneous radioenzymatic determination of plasma and tissue adrenaline, noradrenaline and dopamine within the femtomole range. Life Sci.19 (1976) 1161–1174.

    Article  PubMed  Google Scholar 

  31. Da Prada, M., Bonetti, E.P., and Keller, H.H., Induction of mounting behavior in female and male rats after lisuride. Neurosci. Lett.6 (1977) 349–353.

    Article  PubMed  Google Scholar 

  32. Da Prada, M., Kettler, R., Keller, H.H., and Pieri, M., Einfluss von L-Deprenyl und Ergotderivaten auf das monoaminerge System der Ratte, in: Parkinson-Syndrom: Kombinations- und Begleit-Therapien, pp. 55–73., Ed. P.-A. Fisher. Schattauer Verlag, Stuttgart 1980.

    Google Scholar 

  33. Dreyfus, P.M., and Hauser, G., A simple micromethod for the collection of radioactive carbon dioxide in decarboxylation experiments. Mikrochim. Acta (1964) 150–151.

  34. Duvoisin, R., Mendoza, M.R., Yahr, M.D., and Sweet, R.D., Bromocriptine as an adjuvant to levodopa, in: Dopamiergic ergot derivatives and motor function, pp. 329–335. Eds K. Fuxe and D.B. Calne. Wenner-Gren Center International Sympsoium vol. 31. Pergamon Press, Oxford 1979.

    Chapter  Google Scholar 

  35. Ehinger, H., and Hornykiewicz, O., Verteilung von Noradrenalin und Dopamin im Gehirn des Menschen und ihr Verhalten bei Erkrankungen des extrapyramidalen Systems. Klin. Wschr.38 (1960) 1236–1239.

    Article  Google Scholar 

  36. Fahn, S., The ‘on-off’ phenomenon with levodopa therapy in parkinsonism: clinical and pharmacologic correlations and the effect of intramuscular pyridoxine. Neurology (Minneap.)24 (1974) 431–441.

    Article  CAS  Google Scholar 

  37. Fahn, S., Cormi, R., Snider, S.R., and Prasad, A.L.N., Effect of a catechol-O-methyltransferase inhibitor, U-0521, with levodopa administrtion. Biochem. Pharmac.28 (1979) 1221–1225.

    Article  CAS  Google Scholar 

  38. Fahn, S., Cote, L.J., Snider, S.R., Barrett, R.E., and Isgreen, W.P., Role of bromocriptine in the treatment of parkinsonism, in: Dopaminergic ergot derivatives and motor function, pp. 303–312. Eds K. Fuxe and D.B. Calne. Wenner-Gren Center International Symposium vol. 31. Pergamon Press, Oxford 1979.

    Chapter  Google Scholar 

  39. Fuller, R.W., Clemens, J.A., Kornfeld, E.C., Snoddy, H.D., Smalstig, E.B., and Bach, N.J., Effect of (8β)-8-[(methylthio)methyl]-6-propylergoline on dopaminergic function and brain dopamine turnover in rats. Life Sci.24 (1979) 375–382.

    Article  CAS  PubMed  Google Scholar 

  40. Gauthier, G., de Auriaguerra, J., Simona, B., Constantinidis, J., Eisenring, J.J., Krassoïewitch, M., Yanniatis, G., and Tissot, R., Thérapeutique du syndrome parkinsonien par la L-Dopa associée à des inhibiteurs de la décarboxylase. Revue neurol.122 (1970) 297–319.

    Google Scholar 

  41. Glover, V., Sandler, M., Owen, F., and Riley, G.J., Dopamine is a monoamine oxidase B substrate in man. Nature265 (1977) 80–81.

    Article  CAS  PubMed  Google Scholar 

  42. Goetz, C.G., Tanner, C.M., Glantz, R., and Klawans, H.L., Pergolide in Parkinson's disease. Archs Neurol.40 (1983) 785–787.

    Article  CAS  Google Scholar 

  43. Goldstein, M., Lieberman, A., Lew, J.Y., Asano, T., Rosenfeld, M.R, and Makman, M., Interaction of pergolide with central dopaminergic receptors. Proc. natl Acad. Sci. USA77 (1980) 3725–3728.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Gordonsmith, R.H., Raxworthy, M.J., and Gulliver, P.A., Substrate stereospecificity and selectivity of catechol-O-methyl-transferase for dopa, dopa derivatives and α-substituted catecholamines. Biochem. Pharmac.31 (1982) 433–437.

    Article  CAS  Google Scholar 

  45. Gundert-Reny, U., Hildebradt, R., Stiehl, A., Weber, E., Zürcher, G., and Da Prada, M., Intestinal absorption of levodopa in man. Eur. J. Pharmac.25 (1983) 69–72.

    Article  Google Scholar 

  46. Hornykiewicz, O., Biogenic amines in the central nervous system, in: Handbook of Clinical Neurology, vol. 29. Eds P.J., Vinken and G.W. Bruyn; Metabolic and Deficiency Diseases of the Nervous System, Pard III, pp. 459–483. Ed. H.L. Klawaus. North-Holland, Amsterdam 1977.

    Google Scholar 

  47. Hornykiewicz, O., Biochemical abnormalities in some extrastriatal neuronal systems in Parkinson's disease, in: Parkinson's disease —Current progress, problems and management, pp. 109–119. Eds U.K. Rinne, M. Klingler and G. Stamm. Elsevier/North-Holland, Amsterdam 1980.

    Google Scholar 

  48. Horowski, R., and Wachtel, H., Direct dopaminergic action of lisuride hydrogen maleate, an ergot derivative, in mice. Eur. J. Pharmac.36 (1976) 373–383.

    Article  CAS  Google Scholar 

  49. Horowski, R., and Wachtel, H., Pharmacological effects of lisuride in rodents mediated by dopaminergic receptors: mechanism of action and influence of chronic treatment with lisuride, in: Dopaminergic ergot derivatives and motor function, pp. 237–249. Eds K. Fuxe and D.B. Calne. Wenner-Gren Center International Symposium, vol. 31. Pergamon Press, Oxrord 1979.

    Chapter  Google Scholar 

  50. Johnson, G.A., Baker, C.A., and Smith, R.T., Radioenzymatic assay of sulfate conjugates of catecholamines and DOPA in plasma. Life Sci.26 (1980) 1591–1598.

    Article  CAS  PubMed  Google Scholar 

  51. Karoum, F., Chuang, L.-W., Eisler, T., Calne, D.B., Liebowitz, M.R., Quitkin, F.M., Klein, D.F., and Wyatt, R.J., Metabolism of (−)deprenyl to amphetamine and methamphetamine may be responsible for deprenyl's therapeutic benefit: A biochemical assessment. Neurology32 (1982) 503–509.

    Article  CAS  PubMed  Google Scholar 

  52. Kebabian, J. W., and Calne, D. B., Multiple receptors for dopamine. Naturology32 (1982) 503–509.

    Google Scholar 

  53. Kebabian, J. W., Kebabian, P. R., Munemura, M., and Calne, D. B. Dopaminergic ergots: drugs which discriminate between the multiple classes of dopamine receptors, in: Dopaminergic ergot derivatives and motor function, pp. 61–71. Eds K. Fuxe and D. B. Calne. Wenner-Gren Center International Symposium. Vol. 31. Pergamon Press, Oxford 1979.

    Chapter  Google Scholar 

  54. Kehr, W., Effect of lisuride and other ergot derivatives on monoaminergic mechanisms in rat brain. Eur. J. Pharmac.41 (1977) 261–273.

    Article  CAS  Google Scholar 

  55. Kehr, W., Neumeister, R., and Zimmerman, R., Action of ergot dopaminergic agonists on monoamine synthesis in rat brain, in: Dopaminergic ergot derivatives and motor function, pp. 173–186. Eds K. Fuxe and D. B. Calne. Wenner-Gren Center International Symposium, vol. 31. Pergamon Press, Oxford 1979.

    Chapter  Google Scholar 

  56. Keller, H. H., Burkard, W. P., Pieri, L., Bonetti, E. P., and Da Prada, M., Lisuride- and LSD-induced changes of monoamine turnover in the rat brain. Adv. Biochem. Psychopharmac.19 (1978) 393–396.

    CAS  Google Scholar 

  57. Keller, H. H., Bonetti, E. P., Pieri, L., and Da Prada, M., Lisuride-induced mounting behavior and effects on the monoaminergic system in rat brain, in: Lisuride and other dopamine agonists, pp. 79–87. Eds B. D. Calne, R. Horowski, R. J. McDonald and W. Wuttke. Raven Press, New York 1983.

    Google Scholar 

  58. Knoll, J., and Magyar, K., Some puzzling pharmacological effects of monoamine oxidase inhibitors. Adv. Biochem. Pharmacol.5 (1972) 393–408.

    CAS  Google Scholar 

  59. Knoll, J., The pharmacology of selective irreversible monoamine oxidase inhibitors, in: Enzyme activated irrversible inhibitors, pp. 253–269. Eds N. Seiler, M. J. Jung and J. Koch-Weser. Elsevier-North Holland, Amsterdam 1978.

    Google Scholar 

  60. Knoll, J., (−)Deprenyl: the MAO inhibitor without the cheese effect. Trends Neurosci.2 (1979) 111–113.

    Article  Google Scholar 

  61. Koller, W. C., Weiner, W. J., Diamond, B. I., Nansieda, P. A., and Klawans, H. L., The pharmacological evaluation of pergolide mesylate as a potential antiparkinson agent. Neuropharmacology19 (1980) 831–837.

    Article  CAS  PubMed  Google Scholar 

  62. Kostowski, W., Jerlicz, M., Bidzinski, A., and Hauptmann, M., Evidence for existence of two opposite noradrenergic brain systems controlling behavior. Psychopharmacologia, Berlin59 (1978) 311–312.

    Article  CAS  Google Scholar 

  63. Kuruma, I., Bartholini, G., Tissot, R., and Pletscher, A., Comparative investigation of inhibitors of extracerebral dopa decarboxylase in man and rats. J. Pharm. Pharmac.24 (1972) 289–294.

    Article  CAS  Google Scholar 

  64. Larsen, T. A., and Calne, D. B., Recent advances in the study of Parkinson's disease. Trends Neurosci.5 (1982) 10–12.

    Article  Google Scholar 

  65. Lees, A. J., Kohout, L. J., Shaw, K. M., Stern, G. M., Elsworth, J. D., Sandler, M., and Youdim, M. B. H., Deprenyl in Parkinson's disease. Lancet2 (1977) 65–69.

    Google Scholar 

  66. Lees, A. J., and Stern, G. M., Sustained low-dose levodopa therapy in Parkinson's disease: a 3-year follow-up, in: Advances in Neurology Vol. 37, Experimental therapeutics of movement disorders, pp. 9–15. Eds S. Fahn, D. B. Calne and I. Shoulson. Raven Press, New York 1983.

    Google Scholar 

  67. Le Witt, P. A., and Calne, D. B., Recent advances in the treatment of Parkinson's disease: the role of bromocriptine. J. neural. Transm.51 (1981) 175–184.

    Article  PubMed  Google Scholar 

  68. Le Witt, P. A., Gopinatham, G., Ward, C. D., Sanes, J. N., Dambrosia, J. M., Durso, R., and Calne, D. B., Lisuride versus bromocriptine treatment in Parkinson disease: a double-blind study. Neurology32 (1982) 69–72.

    Article  Google Scholar 

  69. Le Witt, P. A., Burns, R. S., and Calne, D. B., Lisuride treatment in Parkinson's disease: clinical and pharmacokinetic studies, in: Advances in Neurology Vol. 37, Experimental therapeutics of movement disorders, pp. 131–140. Eds S. Fahn, D. B. Calne and I. Shoulson. Raven Press, New York 1983.

    Google Scholar 

  70. Lieberman, A., Goodgold, A., and Jonas, S., Comparison of dopa decarboxylase inhibitor (carbidopa) combined with levodopa and levodopa alone in Parkinson's disease. Neurology (Minneap.)25 (1975) 911–916.

    Article  CAS  Google Scholar 

  71. Lieberman, A., Kupersmith, M., Estey, E., and Goldstein, M., Treatment of Parkinson's disease with bromicriptine. N. Engl. J. Med.295 (1976) 1400–1404.

    Article  CAS  PubMed  Google Scholar 

  72. Lieberman, A., Goldstein, M., Leibowitz, M., Neophytides, A., Kupersmith, M., Pact, V., and Kleinberg, D., Treatment of advanced Parkinson disease with pergolide. Neurology31 (1981) 675–682.

    Article  CAS  PubMed  Google Scholar 

  73. Lieberman, A., Goldstein, M., Neophytides, A., Kupersmith, M., Leibowitz, M., Zasorin, N., Walker, R., and Kleinberg, D., Lisuride in Parkinson disease: efficacy of lisuride compared to levodopa. Neurology31 (1981) 961–965.

    Article  CAS  PubMed  Google Scholar 

  74. Lieberman, A., Neophytides, A., Leibowitz, M., Gopinathan, G., Pact, V., Walker, R., Goodgold, A., and Goldstein, M., Comparative efficacy of pergolide and bromocriptine in patients with advanced Parkinson's disease, in: Advances in Neurology vol. 37, Experimental therapeutics of movement disorders, pp. 95–108. Eds S. Fahn, D. B. Calne and I. Shoulson. Raven Press, New York 1983.

    Google Scholar 

  75. Markstein, R., Herrling, P. L., Bürki, H. R., Asper, H., and Ruch, W., The effect of bromocriptine on rat striatal adenylate cyclase and rat brain monoamine metabolism. J. Neurochem.31 (1978) 1163–1172.

    Article  CAS  PubMed  Google Scholar 

  76. Marsden, C. D., Parkes, J. D., and Rees, J. E., A comparison of treatment of Parkinson's disease with L-DOPA and with SinemetR, in: Current concepts in the treatment of Parkinsonism, pp. 21–35. Ed. M. D. Yahr. Raven Press, New York 1974.

    Google Scholar 

  77. Marsden, C. D., and Parkes, J. D., On-off' effects in patients with Parkinson's disease on chronic levodopa therapy. Lancet1 (1976) 292–296.

    Article  CAS  PubMed  Google Scholar 

  78. McLellan, D. L., and Dean, B. C., Improved control of brittle Parkinsonism by separate administration of levodopa and benserazide. Br. med. J.284 (1982) 1001–1002.

    Article  CAS  Google Scholar 

  79. Narabayashi, H., Pharmacological basis of akinesia in Parkinson's disease. J. neural Transm., suppl. 19 (1983) 143–151.

    Google Scholar 

  80. Papavasiliou, P. S., Cotzias, G. C., and Duby, S. E., Levodopa in Parkinsonism: Potentiation of central effects with a peripheral inhibitor. N. Engl. J. Med.285 (1972) 8–14.

    Article  Google Scholar 

  81. Parkes, J. D., Adverse effects of antiparkinsonian drugs. Drugs21 (1981) 341–353.

    Article  CAS  PubMed  Google Scholar 

  82. Parkes, J. D., Tarsy, D., Marsden, C. D., Bovill, K. T., Phipps, J. A., Rose, P., and Asselman, P., J. Neurol. Neurosurg. Psychiat.38 (1975) 232–237.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Pieri, L., Keller, H. H., Burkard, W. P., and Da Prada, M., Effects of lisuride and LSD on cerebral monoamine systems and hallucinosis. Nature272 (1978) 278–280.

    Article  CAS  PubMed  Google Scholar 

  84. Pieri, L., Keller, H. H., Laurent, J.-P., Burkard, W., Pieri, M., Bonetti, E. P., and Da Prada, M., Behavioural, neurochemical and electrophysiological effects of lisuride and LSD in animals, in: Lisuride and other dopamine agonists, pp. 89–96. Eds D. B. Calne, R. Horowski, R. J. McDonald and W. Wuttke. Raven Press, New York 1983.

    Google Scholar 

  85. Pieri, M., Pieri, L., Saner, A., Da Prada, M., and Haefely, W., A. comparison of drug-induced rotation in rats lesioned in the medial forebrain bundle with 5,6-dihydroxytryptamine or 6-hydroxydopamine. Archs int. Pharmacodyn. Ther.217 (1975) 118–130.

    CAS  Google Scholar 

  86. Pieri, M., Schaffner, R., Pieri, L., Da Prada, M., and Haefely, W., Turning in MFB-lesioned rats and antagonism of neuroleptic-induced catalepsy after lisuride and LSD. Life Sci.22 (1978) 1115–1121.

    Article  Google Scholar 

  87. Pletscher, A., Effect of inhibitors of extracerebral decarboxylase on levodopa metabolism. Adv. Neurol.3 (1973) 49–58.

    CAS  Google Scholar 

  88. Rabey, J. M., Passettiner, P., Bystritsky, A., Engel, J., and Goldstein, M., The regulation of striatal DOPA synthesis by α2-adrenoceptors. Brain Res.230 (1981) 422–426.

    Article  CAS  PubMed  Google Scholar 

  89. Raches, A., and Fahn, S., O-Methyldopa interferes with striatal utilization of levodopa. Ann. Neurology10 (1981) 94–95.

    Google Scholar 

  90. Reynolds, G. P., Riederer, P., and Sandler, M., Amphetamine and 2-phenylethylamine in post-mortem parkinsonian brain after (−)deprenyl administration. J. neural Transm.43 (1978) 271–277.

    Article  CAS  PubMed  Google Scholar 

  91. Reynolds, G. P., Riederer, P., and Rausch, W.-D., Dopamine metabolism in human brain: effects of monoamine oxidase inhibition in vitro by (−)deprenyl and (+) and (−)tranylcypromine. J. neural Transm., suppl. 16 (1980) 173–178.

    Google Scholar 

  92. Riederer, P., Jelliger, K., Danlerczyk, W., Seemann, D., Ulm, G., Reynolds, G. P., Birkmayer, W., and Koppel, H., Combination treatment with selective monoamine oxidase inhibitors and dopaminergic agonists in Parkinson's disease: biochemical and clinical observations, in: Advances in Neurology Vol. 37, Experimental therapeutics of movement disorders, pp. 159–176. Eds S. Fahn, D. B. Calne and I. Shoulson. Raven Press, New York 1983.

    Google Scholar 

  93. Rinne, U. K., Siirtola, T., and Sonninen, V., L-Deprenyl treatment of on-off phenomena in Parkinson's disease. J. neural. Transm.43 (1978) 253–262.

    Article  CAS  PubMed  Google Scholar 

  94. Rinne, U. K., Martilla, R., and Sonninen, V., Relationship between brain dopamine turnover and therapeutic response to bromocriptine, in: Dopaminergic ergot derivatives and motor function, pp. 319–324, Eds K. Fuxe and D. B. Calne. Wenner-Gren Center International Symposium, vol. 31. Pergamon Press, Oxford 1979.

    Chapter  Google Scholar 

  95. Rinne, U. K., and Mölsä, P., Levodopa with benserazide or carbidopa in Parkinson disease. Neurology29 (1979) 1584–1589.

    Article  CAS  PubMed  Google Scholar 

  96. Rinne, U. K., Klingler, M., and Stamm, G., eds, Parkinson's disease—Current progress, problems and management. Elsevier/North-Holland, Amsterdam 1980.

    Google Scholar 

  97. Rinne, U. K., Koskinen, V., and Lönnberg, P., Neurotransmitter receptors in the parkinsonian brain, in: Parkinson's disease—Current progress, problems and management, pp. 93–107. Eds U. K. Rinne, M. Klingler and G. Stamm. Elsevier/North-Holland, Amsterdam 1980.

    Google Scholar 

  98. Rinne, U. K., Treatment of Parkinson's disease: problems with a progressing disease. J. neural Transm.51 (1981) 161–174.

    Article  CAS  PubMed  Google Scholar 

  99. Rinne, U. K., Dopamine agonists in the treatment of Parkinson's disease, in: Advances in neurology Vol. 37, Experimental therapeutics of movement disorders, pp. 141–150. Eds S. Fahn, D. B. Calne and I. Shoulson. Raven Press, New York 1983.

    Google Scholar 

  100. Sandler, M., Glover, V., Ashford, A., and Stern, G. M., Absence of cheese-effect during deprenyl therapy: some recent studies. J. neural Transm.43 (1978) 209–215.

    Article  CAS  PubMed  Google Scholar 

  101. Scatton, B., Effect of dopamine agonists and neuroleptic agents on striatal acetylcholine transmission in the rat: evidence against dopamine receptor multiplicity. J. Pharmac. exp. Ther.220 (1982) 197–220.

    CAS  Google Scholar 

  102. Schachter, M., Bedard, P., Debono, A. G., Jenner, P., Marsden, C. D., Price, P., Parkes, J. D., Keeman, J., Smith, B., Rosenthaler, J. J., Horowski, R., and Dorow, R., The role of D1 and D2 receptors. Nature, Lond.286 (1980) 157–159.

    Article  CAS  PubMed  Google Scholar 

  103. Seeman, P., Brain dopamine receptors. Pharmac. Rev.32 (1980) 230–287.

    Google Scholar 

  104. Sethy, V. H., Regulation of striatal acetylcholine concentration by D2-dopamine receptors. Eur. J. Pharmac.60 (1979) 397–398.

    Article  CAS  Google Scholar 

  105. Siegfried, J., Klaiber, R., Perret, E., and Ziegler, W. H., Behandlung des Morbus Parkinson mit L-Dopa in Kombination mit einem Decarboxylaschemmer. Dt. med. Wschr.94 (1969) 2678.

    Article  CAS  Google Scholar 

  106. Silbergeld, E. K., Hruska, R. E., Weir, R., and Kennedy, S. W., Dopaminergic and serotoninergic effects of ergot drugs, in: Dopaminergic ergot derivatives and motor function, pp. 223–235. Eds K. Fuxe and D. B. Calne. Wenner-Gren Center International Symposium, vol. 31. Pergamon Press, Oxford 1979.

    Chapter  Google Scholar 

  107. Simpson, L. L., Evidence that deprenyl, a type B monoamine oxidase inhibitor, is an indirectly acting sympathomimetic amine. Biochem. Pharmac.27 (1978) 1591–1595.

    Article  CAS  Google Scholar 

  108. Thorner, M. D., Flückiger, E., and Calne, D. B., Bromocriptine—A clinical and pharmacological review. Raven Press, New York 1980.

    Google Scholar 

  109. Tissot, R., Eisenring, J.-J., and Constantinidis, J., Modes of action and optimal dosage of decarboxylase inhibitors, in: Current concepts in the treatment of Parkinsonism, pp. 123–132. Ed. M. D. Yahr. Raven Press, New York 1974.

    Google Scholar 

  110. Ungerstedt, U., and Arbuthnott, G. W., Quantitative recording of rotational behavior in rats after 6-OH-dopamine lesions of the nigrostriatal system. Brain Res.24 (1970) 485–493.

    Article  CAS  PubMed  Google Scholar 

  111. Ungerstedt, U., Avemo, A., Avemo, E., Ljungberg, T., and Ranje, C., Animal models of Parkinsonism, in: Advances in Neurology, vol. 3, pp. 257–271. Ed. D. B. Calne. Raven Press, New York 1973.

    Google Scholar 

  112. Yahr, M. D., Duvoisin, R. C., and Mendoza, M. R., Modification of L-Dopa therapy of parkinsonism by alpha-methyldopa hydrazine (MK-486). Trans. Am. neurol. Assoc.96 (1971) 55–58.

    CAS  PubMed  Google Scholar 

  113. Yahr, M. D., Overview of present day treatment of Parkinson's disease. J. neural Transm.43 (1978) 227–238.

    Article  CAS  PubMed  Google Scholar 

  114. Zürcher, G., and Da Prada, M., Radioenzymatic assay of femtomole concentrations of DOPA in tissues and body fluids. J. Neurochem.33 (1979) 631–639.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Da Prada, M., Keller, H.H., Pieri, L. et al. The pharmacology of Parkinson's disease: Basic aspects and recent advances. Experientia 40, 1165–1172 (1984). https://doi.org/10.1007/BF01946641

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01946641

Key words

Navigation