Advertisement

Parkinsonism

Physiology and Pharmacology
  • Richard P. Newman
  • Donald B. Calne

Abstract

Major advances have been made in the last two decades in understanding the biochemical pharmacology and pathophysiology of Parkinson’s disease. The value of levodopa as the mainstay for chronic therapy of parkinsonism is well established. Aspects of the cardinal features of parkinsonism, rigidity, tremor, and bradykinesia, have become better elucidated by physiological analysis. Recent insights into receptor mechanisms provide new approaches to pharmacotherapy.

Keywords

Dopamine Receptor Essential Tremor Tardive Dyskinesia Prolactin Release Ergot Derivative 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Agnoli, A., Ruggieri, S., Falaschi, P., Mearelli, S., DelRoscio, S., D’Urso, R., and Frajes, G., 1980, Are the enkephalins involved in Parkinson’s disease? Clinical and neuroendocrine responses to naloxone administration, in: Neural Peptides and Neuronal Communication ( E. Costa and M. Trabucchi, eds.), pp. 511–521, Raven Press, New York.Google Scholar
  2. Andrews, C. J., Neilson, P. D., and Lance, J. W., 1973, Comparison of stretch reflexes and shortening reactions in activated normal subjects with those in Parkinson’s disease, J. Neurol. Neurosurg. Psychiatry 36: 329–333.PubMedCrossRefGoogle Scholar
  3. Baldessarini, R. J., and Tarsy, D., 1978, Tardive dyskinesia, in: Psychopharmacology: A Generation of Progress ( M. A. Lipton, A. DiMascio, and K. F. Killam, eds.), pp. 993–1004, Raven Press, New York.Google Scholar
  4. Berger, P. A., and Rexroth, K., 1980, Tardive dyskinesia: Clinical, biological, and pharmacological perspectives, Schizophrenia Bull. 6: 102–116.Google Scholar
  5. Brown, E. M., Carroll, R. J., and Aurbach, G. D., 1977, Dopaminergic stimulation of cyclic AMP accumulation and parathyroid hormone release from dispersed bovine parathyroid cells, Proc. Natl. Acad. Sci. USA 74: 4210–4213.PubMedCrossRefGoogle Scholar
  6. Burke, D., and Lance, J. W., 1973, Studies of the reflex effects of primary and secondary spindle endings in spasticity, in: New Developments in Electromyography and Clinical Neurophysiology, Vol. 3 ( J. E. Desmedt, ed.), pp. 479–495, Karger, Basel.Google Scholar
  7. Burns, R. S., and Calne, D. B., 1981, Treatment of parkinsonism with artificial dopaminomimetics: Pharmacokinetic considerations, in: Apomorphine and Other Dopamnnomimetics, Vol. 2, Clinical Pharmacology ( G. U. Corsini and G. L. Gessa, eds.), pp. 93–106, Raven Press, New York.Google Scholar
  8. Burns, R. S. Chiueh, C. C., Markey, S. P., Ebert, M. H., Jacobowitz, D. M., and Kopin, I. J., 1983, 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-tetrahydropteridine, Proc. Natl. Acad. Sci. USA 80: 4546–4550.PubMedCrossRefGoogle Scholar
  9. Burns, R. S., Markey, S. P., Phillips, J. M., and Chiueh, C. C., 1984, The neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropteridine in the monkey and man, Can. J. Neurol. Sci. 11: 166–168.PubMedGoogle Scholar
  10. Cannon, J. G., Costall, B., Laduron, P. M., Leysen, J. E., and Naylor, R. J., 1978, Effects of some derivatives of 2-aminotetralin on dopamine-sensitive adenylate cyclase and the binding of (3-H)-haloperidol to neuroleptic receptors in the rat striatum, Biochem. Pharmacol. 27: 1417–1420.PubMedCrossRefGoogle Scholar
  11. Clark, M. L., Huber, W. K., Sakata, K., Fowles, D. C., and Serafetinides, E. A., 1970, Molindone in chronic schizophrenia, Clin. Pharmacol. Ther. 11: 680–688.PubMedGoogle Scholar
  12. Corrodi, H., Fuxe, K., Hokfelt, T., Lidbrink, P., and Ungerstedt, U., 1973, Effects of ergot drugs on central catecholamine neurons: Evidence for a stimulation of central dopamine neurons. J. Pharm. Pharmacol. 25: 409–412.PubMedCrossRefGoogle Scholar
  13. Corsini, G. U., Piccardi, M. P., Bocchetta, A., Bernardi, F., and Del Zompo, M., 1981, Behavioral effects of apomorphine in man: Dopamine receptor implication, in: Apomorphine and Other dopaminomimetics, Vol. 2, Clinical Pharmacology ( G. U. Corsini and G. L. Gessa, eds.), pp. 13–24, Raven Press, New York.Google Scholar
  14. Cote, T., Munemura, M., and Kebabisn, J., 1979, Lisuride hydrogen maleate: An ergoline with beta-adrenergic antagonist activity, Eur. J. Pharmacol. 59: 303–306.PubMedCrossRefGoogle Scholar
  15. Cote, T. E., Grewe, C. W., and Kebabian, J. W., 1981, Stimulation of a D-2 dopamine receptor in the intermediate lobe of the rat pituitary gland decreases the responsiveness of the betaadrenoceptor: Biochemical mechanism, Endocrinology 108: 420–426.PubMedCrossRefGoogle Scholar
  16. Crane, G. E., 1971, Persistence of neurological symptoms due to neuroleptic drugs, Am. J. Psychiat. 127: 143–146.Google Scholar
  17. Creese, I., Sibley, D. R., Leff, S., and Hamblin, M., 1981, Dopamine receptors: Subtypes, localization, and regulation, Fed. Proc. 40: 147–152.PubMedGoogle Scholar
  18. Cross, A. J., and Owen, F., 1980, Characteristics of 3-H-cis-flupenthixol binding to calf brain membranes, Eur. J. Pharmacol. 65: 341–347.PubMedCrossRefGoogle Scholar
  19. Dejerine, J., 1914, Semeiologie des Affections du Systeme Nerveux, p. 464, Masson, Paris.Google Scholar
  20. Duvoisin, R. C., 1976, Digital vasospasm with bromocriptine, Lancet, 2: 204.PubMedCrossRefGoogle Scholar
  21. Eisler, T., Hall, R. P., Kalavar, K. A. R., and Calne, D. B., 1981, Erythromelalgia-like eruption in parkinsonian patients treated with bromocriptine, Neurology 31: 1368–1370.PubMedGoogle Scholar
  22. Elliot, P. N. C., Jenner, P., and Marsden, C. D., 1981, Akinesia, physiologic rest mechanisms, opiates, and the basal ganglia, in: Research Progress in Parkinson’s Disease ( F. C. Rose and R. Capildes, eds.), pp. 98–104, Pittman Medical Ltd., Kent, Great Britain.Google Scholar
  23. Euvrard, C., Premont, J., Oberlander, C., Boissier, J. R., and Bockaert, J., 1979, Is dopamine-sensitive adenylate cyclase involved in regulating the activity of striatal cholinergic neurons? Naunyn. Schmiedeberg. Arch. Pharmacol. 309: 241–245.CrossRefGoogle Scholar
  24. Flowers, K. A., 1976, Visual `closed loop’ and `open-loop’ characteristics of voluntary movement in patients with parkinsonism and intention tremor, Brain 99: 269–310.PubMedCrossRefGoogle Scholar
  25. Garnett, E. S., Nahmias, C., and Firnau, G., 1984, Central dopaminergic pathways in hemiparkinsonism examined by positron emmision tomography, Can. J. Neurol. Sci. 11: 174–179.PubMedGoogle Scholar
  26. Goldstein, M., Lieberman, A., Lew, J. Y., Asano, T., Rosenfeld, M. R., and Makman, M. H., 1980, Interaction of pergolide with central dopaminergic receptors, Proc. Natl. Acad. Sci. USA 77: 3725–3728.PubMedCrossRefGoogle Scholar
  27. Gopinathan, G., and Caine, D. B., 1980, Incontinence of urine with long-term bromocriptine therapy, Ann. Neurol. 8: 204.PubMedCrossRefGoogle Scholar
  28. Gopinathan, G., Teravainen, H., Dambrosia, J. M., Ward, C. D., Sanes, J. N., Stuart, W. K.Evarts, E. V., and Caine, D. B., 1981, Lisuride in parkinsonism, Neurology 31: 371–376.Google Scholar
  29. Grimes, J. D., 1984, Bromocriptine in Parkinson’s disease: Results obtained with high and low dose therapy, Can. J. Neurol. Sci. 11: 225–228.PubMedGoogle Scholar
  30. Hallett, M., and Khoshbin, S., 1980, A physiological mechanism of bradykinesia, Brain 103: 301–314.PubMedCrossRefGoogle Scholar
  31. Hauth, H., 1979, Chemical aspects of ergot derivative with central dopaminergic activity, in: Dopaminergic Ergots and Motor Function ( K. Fuxe and D. B. Caine, eds.), pp. 23–32, Pergamon Press, Oxford.Google Scholar
  32. Izumi, K., Motomatsu, T., Chretien, M., Butterworth, R. F., Lis, M., Seidah, N., and Barbeau, A., 1977, Beta-endorphin induced akinesia in rats: Effect of apomorphine and alpha-methylp-tyrosine and related modifications of dopamine turnover in the basal ganglia, Life Sci. 20: 1149–1156.PubMedCrossRefGoogle Scholar
  33. Jankovic, J., and Frost, J. D., 1981, Quantitative assessment of parkinsonian and essential tremor: Clinical application of triaxial accelerometry, Neurology 31: 1235–1240.PubMedGoogle Scholar
  34. Jeste, D. V. and Wyatt, R. J., 1979, In search of treatment for tardive dyskinesia: Review of the literature. Schizophrenia Bull. 5: 251–293.Google Scholar
  35. Kebabian, J. W.. and Caine, D. B., 1979, Multiple receptors for dopamine, Nature (London) 277: 93–96.CrossRefGoogle Scholar
  36. Kebabian, J. W. and Cote, T. E., 1981, Dopamine receptors and cyclic AMP: A decade of progress, Trends Pharmacol. Sci. 2: 69–71.CrossRefGoogle Scholar
  37. Kolbe, H., Clow, A., Jenner, P., and Marsden, C. D., 1981, Neuroleptic-induced acute dystonic reactions may be due to enhanced dopamine release on to supersensitive postsynaptic receptors, Neurology 31: 434–439.PubMedGoogle Scholar
  38. Koller, W. L., Weiner, W. J., Diamond, B. I., Nausieda, P. A., and Klawans, H. L., 1980, The pharmacologic evaluation of pergolide mesylate as a potential anti-parkinsonian agent, Neuropharmacology 19: 831–837.PubMedCrossRefGoogle Scholar
  39. Korczyn, A. D., 1978, The pathophysiology of dystonia, J. Neural Transm. 42:245–250. Langston, J. W., Ballard, P., Tetrud, J. W., and Irwin, I., 1983, Chronic parkinsonism in humans due to a product of meperidine-analog synthesis, Science 219: 979–980.Google Scholar
  40. Larsen, T. A., Newman, R., LeWitt, P., and Caine, D. B., 1984, Severity of Parkinson’s disease and the dosage of bromocriptine, Neurology 34: 795–797.PubMedGoogle Scholar
  41. Lemberger, L. and Crabtree, R. E., 1979, Pharmacologic effects in man of a potent, long acting dopamine receptor agonist, Science 205: 1151–1152.PubMedCrossRefGoogle Scholar
  42. LeWitt, P. A. and Caine, D. B., 1981, Recent advances in the treatment of Parkinson’s disease: The role of bromocriptine, J. Neural Transm. 51: 175–184.CrossRefGoogle Scholar
  43. LeWitt, P. A., Ward, C. D., Larsen, T. A., Raphaelson, M. I., Newman, R. P., Foster, N. L., Dambrosia, J., and Caine, D. B., 1983, Comparison of pergolide and bromocriptine therapy in parkinsonism, Neurology, 33: 1009–1014.PubMedGoogle Scholar
  44. Lieberman, A., Goldstein, M., Liebowitz, M., Neophytides, A., Kupersmith, M., Pact, V., and Kleinberg, D., 1981, Treatment of advanced Parkinson disease with pergolide, Neurology 31: 675–682.PubMedGoogle Scholar
  45. Markstein, R., 1981, Neurochemical effects of some ergot derivatives: A basis for their antiparkinsonian actions, J. Neural Transm. 51: 39–59.PubMedCrossRefGoogle Scholar
  46. Martin, W. R. W., Beckman, J. H., Caine, D. B., Adam, M. J., Harrop, R., Rogers, J. G., Ruth, T. J., Sayre, C. I., and Pate, B. D., 1984, Cerebral glucose metabolism in Parkinson’s disease, Can. J. Neurol. Sci. 11: 169–173.PubMedGoogle Scholar
  47. Menon, M. K., Clark, W. G., and Neurmeyer, J. L., 1978, Comparison of the dopaminergic effects of apomorphine and (-)-N-n-propylnorapomorphine, Eur. J. Pharmacol. 52: 1–9.PubMedCrossRefGoogle Scholar
  48. Moore, K. E., and Kelly, P. H., 1978, Biochemical pharmacology of mesolimbic and mesocortical dopaminergic neurons, in: Psychopharmacology: A Generation of Progress ( M. A. Lipton, A. DiMascio, and K. F. Killam, eds.), pp. 221–234. Raven Press, New York.Google Scholar
  49. Nasrallah, H. A., 1980, Neuroleptic plasma levels and tardive dyskinesia: A possible link? Schizophrenia Bull. 6: 4–7.Google Scholar
  50. Nutt, J. G., Rosin, A. J., Eisler, T., Caine, D. B., and Chase, T. N., 1978, Effect of an opiate antagonist on movement disorders, Arch. Neurol. 35: 810–811.PubMedCrossRefGoogle Scholar
  51. Pert, C. B., Kuhar, M. J., and Snyder, S. H., 1976, Opiate receptors: Autoradiographic localization in rat brain, Proc. Natl. Acad. Sci. USA 73: 3729–3733.PubMedCrossRefGoogle Scholar
  52. Pieri, L., Pieri, M., and Haefely, W., 1974, LSD as an agonist of dopamine receptors in the striatum, Nature (London) 252: 586–588.CrossRefGoogle Scholar
  53. Price, P., Baxter, R. C. H., Parkes, J. D., and Marsden, C. D., 1979, Opiate antagonists and Parkinson’s disease, Arch. Neurol. 36: 661.PubMedCrossRefGoogle Scholar
  54. Quinn, N., Illas, A., L’Hermitte, F., and Agid, Y., 1981, Bromocriptine and domperidone in the treatment of Parkinson’s disease, Neurology 31: 662–667.PubMedGoogle Scholar
  55. Reisine, T. D., Rossor, M., Spokes, E., Iversen, L. L., and Yamamura, H. I., 1979, Alterations in brain opiate receptors in Parkinson’s disease, Brain Res. 173: 378–382.PubMedCrossRefGoogle Scholar
  56. Rondot, P., and Bathien, N., 1978, Pathophysiology of parkinsonian tremor, in: Progress in Clinical Neurophysiology, Vol. 5, Physiological Tremor, Pathological Tremors, and Clonus ( J. E. Desmedt, ed.), pp. 138–149, Karger, Basel.Google Scholar
  57. Rondot, P., Jednyak, C. P., and Ferry, G., 1978, Pathological tremors: Nosological correlates, in: Progress in Clinical Neurophysiology, Vol. 5, Physiological Tremor, Pathological Tremors and Clonus ( J. E. Desmedt, ed.), pp. 95–113, Karger, Basel.Google Scholar
  58. Schachter, M., Bedard, P., Debono, A. G., Jenner, P., Marsden, C. D., Price, P., Parkes, J. D., Keenan, J., Smith, B., Rosenthaler, J., Horowski, R., and Dorow, R., 1980, The role of DI and D-2 receptors, Nature (London) 286: 137–138.CrossRefGoogle Scholar
  59. Schwab, R. S., Amados, L. V., and Lettvian, J. U., 1951, Apomorphine in Parkinson’s disease, Trans. Am. Neurol. Assoc. 76: 251–253.Google Scholar
  60. Segal, D., Browne, R. G., Bloom, F., Ling, N., and Guillemin, R., 1977, Beta-endorphin: Endogenous opiate or neuroleptic? Science 198: 411–413.PubMedCrossRefGoogle Scholar
  61. Seiler, P. E., Sarau, H. M., Zirkle, C. L., and Saunders, H. L., 1978, The central effects of a novel dopamine agonist, Eur. J. Phamacol. 50: 419–430.CrossRefGoogle Scholar
  62. Shibuya, M., 1979, Dopamine-sensitive adenylate cyclase activity in the striatum in Parkinson’s disease, J. Neural Transm. 44: 287–295.PubMedCrossRefGoogle Scholar
  63. Simantov, R., Kuhar, M. J., Pasternak, G. W., and Snyder, S. H., 1976, The regional distribution of a morphine-like factor enkephalin in monkey brain, Brain Res. 106: 189–197.PubMedCrossRefGoogle Scholar
  64. Sokoloff, P., Martres, M. P., and Schwartz, J. C., 1980, Three classes of dopamine receptor (D2, D-3, D-4) identified by binding studies with 3-H-apomorphine and 3-H-domperidone, Naunyn-Schmiedeberg Arch. Pharmacol. 315: 89–102.CrossRefGoogle Scholar
  65. Sovner, R. and DiMascio, A., 1978, Extrapyramidal syndromes and other neurological side effects of psychotropic drugs, in: Psychopharmacology: A Generation of Progress ( M. A. Lipton, A. DiMascio, and K. F. Killam, eds.), pp. 1021–1032, Raven Press, New York.Google Scholar
  66. Spano, P. F., Frattola, L., Govoni, S., Tonon, G. C., and Trabucchi, M., 1979, Dopaminergic ergot derivatives: Selective agonists of a new class of dopamine receptors, in: Dopaminergic Ergot Derivatives and Motor Functions ( K. Fuxe and D. B. Caine, eds.), pp. 159–171, Pergamon Press, Oxford.Google Scholar
  67. Stoof, J. C., Thieme, R. E., Vrijmoed de Vries, M. C., and Mulder, A. H., 1979, In vitro acetylcholine release from rat caudate nucleus as a new model for testing drugs with dopamine receptor activity, Naunyn-Schmiedeberg Arch. Pharmacol. 309: 119–124.CrossRefGoogle Scholar
  68. Struppler, A., Erbel, F., and Velho, F., 1978, An overview of the pathophysiology of parkinsonian and other pathological tremors, in: Progress in Clinical Neurophysiology, Vol. 5, Physiologic Tremor, Pathologic Tremors, and Clonus ( J. E. Desmedt, ed.), pp. 114–128, Karger, Basel.Google Scholar
  69. Sulser, F., and Robinson, S. E., 1978, Clinical implications of pharmacologic differences among antipsychotic drugs with particular emphasis on biochemical central synaptic mechanisms, in: Psychopharmacology: A Generation of Progress ( M. A. Lipton, A. DiMascio and K. F. Killam, eds.), pp. 943–954, Raven Press, New York.Google Scholar
  70. Tamminga, C. A., DeFraites, E. G., Gotts, M. D., and Chase, T. N., 1981, Apomorphine and Nn-propylnorapomorphine in treatment of schizophrenia, in: Apomorphine and Other Dopaminomimetics, Vol. 2, Clinical Pharmacology ( G. U. Corsini and G. L. Gessa, eds.), pp. 4955, Raven Press, New York.Google Scholar
  71. Taquet, H., Javoy-Agid, F., Cesselin, F., and Agid, Y., 1981, Methionine—enkephalin deficiency in brains of patients with Parkinson’s disease, Lancet 1: 1367–1368.PubMedCrossRefGoogle Scholar
  72. Teravainen, H., and Calne, D. B., 1979, Developments in understanding the physiology and pharmacology of parkinsonism, Acta Neurol. Scand. 60: 1–11.PubMedCrossRefGoogle Scholar
  73. Teychenne, P. F., 1983, Parkinson’s disease: The current status of drug treatment: The role of peptides, in: Neurotransmitters and Neuropeptides, Asia Pacific Congress Series No. 24, Exerpta Medica.Google Scholar
  74. Thorner, M. O., Perryman, R. L., Cronin, M., Logan, I. S., Chun, J. K., and MacLeod, R. M., 1981, Dopaminergic drugs in the treatment of prolactin disorders, in: Apomorphine and Other Dopaminomimetics, Vol. 2, Clinical Pharmacology ( G. U. Corsini and R. L. Gessa, eds.), pp. 203–213, Raven Press, New York.Google Scholar
  75. Tolosa, E. S., Cotzias, G. C., Burckhardt, P. G., Tang, L. C., and Dahl, K. E., 1977, The do- paminergic and antidopaminergic effects of some aporphines, Exp. Neurol. 55: 56–66.PubMedCrossRefGoogle Scholar
  76. Tsuruta, K., Frey, E. A., Grewe, C. W., Cote, T. E., Eskay, R. L., and Kebabian, J. W., 1981, Evidence that LY-141865 specifically stimulates the D-2 receptor, Nature (London) 292: 463–469.CrossRefGoogle Scholar
  77. Von Hunger, K., Roberts, S., and Hill, D. F., 1974, LSD as an agonist and antagonist at central dopamine receptors, Nature (London) 252: 588–589.CrossRefGoogle Scholar
  78. Watling, K. J., Dowling, J. E., and Iversen, L. L., 1979, Dopamine receptors in the retina may all be linked to adenylate cyclase, Nature (London) 281: 578–580.CrossRefGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1986

Authors and Affiliations

  • Richard P. Newman
    • 1
  • Donald B. Calne
    • 1
  1. 1.Experimental Therapeutics Branch, National Institute of Neurological and Communicative Disorders and StrokeNational Institutes of HealthBethesdaUSA

Personalised recommendations