Disturbances of synaptic transmission

  • M. J. Eadie
  • J. H. Tyrer


There appears to be more variety in the chemical substances involved in synaptic transmission than in those involved in any other single stage of neuro-physiological activity. This fact is utilized in clinical neuropharmacology, where an attempt is made to alter specific aspects of neural function selectively by pharmacological manipulation of individual neurotransmitters. Unlike the disorders so far considered in this book, disorders of neurotransmitter function all appear to be consequences of other disease processes. The natures of the primary disease processes are usually poorly understood. In general, disorders of synaptic transmission are more frequent and more important clinically than most of the disorders of other neurochemical mechanisms so far dealt with in this book.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Watkins, J. C. and Evans, R. H. (1981). Excitatory amino acid transmitters. Annu. Rev. Pharmacol. Toxicol., 21, 165–204PubMedGoogle Scholar
  2. 2.
    Schwartz, J-C., Pollard, H. and Quach, T. T. (1980). Histamine as a neurotransmitter in mammalian brain: neurochemical evidence. J. Neurochem., 35, 26–35PubMedGoogle Scholar
  3. 3.
    Fredholm, B. B. and Hedquist, P. (1980). Modulation of neurotransmission by purine nucleotides and nucleosides. Biochem. Pharmacol., 29, 1635–1643PubMedGoogle Scholar
  4. 4.
    Calne, D. B. (1979). Neurotransmitters, neuromodulators, and neurohormones. Neurology, 29, 1517–1521PubMedGoogle Scholar
  5. 5.
    O’Dea, R. F., Viveros, O. H. and Diliberto, E. J. Jr. (1981). Protein carboxymethylation: role in the regulation of cell functions. Biochem. Pharmacol., 30, 1163–1168PubMedGoogle Scholar
  6. 6.
    Snyder, S. H. and Goodman, R. R. (1980). Multiple neurotransmitter receptors. J. Neurochem., 35, 5–15PubMedGoogle Scholar
  7. 7.
    Starke, K. (1981). Presynaptic receptors. Annu. Rev. Pharmacol. Toxicol., 21, 7–30PubMedGoogle Scholar
  8. 8.
    Cooper, J. R., Bloom, F. E. and Roth, R. H. (1978). The Biochemical Basis of Neuropharmacology. 3rd Edn. (New York: Oxford University Press)Google Scholar
  9. 9.
    Sterling, G. H. and O’Neill, J. J. (1978). Citrate as the precursor of the acetyl moiety of acetylcholine. J. Neurochem., 31, 525–530PubMedGoogle Scholar
  10. 10.
    Cornford, E. M., Braun, L. D. and Oldendorf, W. H. (1978). Carrier mediated blood-brain barrier transport of choline and certain choline analogs. J. Neurochem., 30, 299–308PubMedGoogle Scholar
  11. 11.
    Kuhar, M. J. and Murrin, L. C. (1978). Sodium-dependent, high affinity choline uptake. J. Neurochem., 30, 15–21PubMedGoogle Scholar
  12. 12.
    Lindstrom, J. and Dau, P. (1980). Biology of myasthenia gravis. Annu. Rev. Pharmacol. Toxicol., 20, 337–362PubMedGoogle Scholar
  13. 13.
    Michelson, M. J. and Danilov, A. F. (1971). Synaptic vesicles, specific granules, autopharma-cology. 5.1. Cholinergic transmissions. In Bacq, Z. M. (ed.) Fundamentals of Biochemical Pharmacology, pp. 221–253. (Oxford: Pergamon)Google Scholar
  14. 13.
    Iversen, L. L. (1974). Uptake mechanisms for neurotransmitter amines. Biochem. Pharmacol., 23, 1927–1935PubMedGoogle Scholar
  15. 15.
    Eadie, M. J. and Tyrer, J. H. (1980). Anticonvulsant Therapy. Pharmacological Basis and Practice. 2nd Edn. (Edinburgh: Churchill-Livingstone)Google Scholar
  16. 16.
    Rowland, L. P. (1978). Myasthenia gravis. In Matthews, W. B. and Glaser, G. H. (eds.) Recent Advances in Clinical Neurology. Vol. 2, pp. 25–46. (Edinburgh: Churchill-Livingstone)Google Scholar
  17. 17.
    Simpson, J. A. (1977). Myasthenia gravis — validation of a hypothesis. Scott. Med. J., 22, 201–210PubMedGoogle Scholar
  18. 18.
    Engel, A. G. and Santa, I. (1971). Histometric analysis of the ultrastructure of the neuromuscular junction in myasthenia gravis and in the myasthenic syndrome. Ann. N. Y. Acad. Sci., 183, 46–63PubMedGoogle Scholar
  19. 19.
    Lindstrom, J. M. and Lambert, E. H. (1978). Content of acetylcholine receptor and antibodies bound to receptor in myasthenia gravis, experimental autoimmune myasthenia gravis and Eaton-Lambert syndrome. Neurology, 28, 130–138PubMedGoogle Scholar
  20. 20.
    Gutmann, L. and Pratt, L. (1976). Pathophysiologic aspects of human botulism. Arch. Neurol., 33, 175–179PubMedGoogle Scholar
  21. 21.
    Wonnacott, S., Marchbanks, R. M. and Fiol, C. (1978). Ca2+ uptake by synaptosomes and its effect on the inhibition of acetylcholine release by botulinium toxin. J. Neurochem., 30, 1127–1134PubMedGoogle Scholar
  22. 22.
    Harris, H. (1970). The Principles of Human Biochemical Genetics. (Amsterdam: North Holland)Google Scholar
  23. 23.
    McMillen, B. A., German, D. C. and Shore, P. A. (1980). Functional and pharmacological significance of brain dopamine and norepinephrine storage pools. Biochem. Pharmacol., 29, 3045–3050PubMedGoogle Scholar
  24. 24.
    Kebabian, J. W. and Calne, D. B. (1979). Multiple receptors for dopamine. Nature (London), 277, 93–96Google Scholar
  25. 25.
    Seeman, P. (1980). Brain dopamine receptors. Pharmacol. Rev., 32, 230–313Google Scholar
  26. 26.
    Creese, I., Sibley, D. R., Leff, S. and Hamblin, M. (1981). Dopamine receptors: subtypes, localization and regulation. Fed. Proc, 40, 147–152PubMedGoogle Scholar
  27. 27.
    Minneman, K. P. and Molinoff, P. B. (1980). Classification and quantitation of β-adrenergic receptor subtypes. Biochem. Pharmacol, 29, 1317–1323PubMedGoogle Scholar
  28. 28.
    Starke, K., Taube, H. D. and Borowski, E. (1977). Presynaptic receptor systems in catechola-minergic transmission. Biochem. Pharmacol, 26, 259–268PubMedGoogle Scholar
  29. 29.
    Demet, E. M. and Halaris, A. E. (1979). Origin and distribution of 3-methoxy-4-hydroxyphenylglycol in body fluids. Biochem. Pharmacol, 28, 3043–3049PubMedGoogle Scholar
  30. 30.
    Ehringer, H. and Hornykewicz, O. (1960). Verteilung von Noradrenalin and Dopamin (3-Hydroxytryptamin) im Gehirn des Menschen und ihr Verhalten bei Erkrankungen des extrapyramidalen Systems. Klin. Wochenschr., 38, 1236–1239PubMedGoogle Scholar
  31. 31.
    Melamed, E., Hefti, F. and Wurtman, R. J. (1980). Nonaminergic striatal neurons convert exogenous L-dopa to dopamine in Parkinsonism. Ann. Neurol, 8, 558–563PubMedGoogle Scholar
  32. 32.
    Poirier, L. J., Filion, M., Larochelle, L. and Pecharde, J-C. (1976). Physiopathology of tremor and rigidity. In Birkmayer, W. and Hornykiewicz, O. (eds.) Advances in Parkinsonism, pp. 217–235. (Basle: Roche)Google Scholar
  33. 33.
    Eadie, M. J. and Sutherland, J. M. (1964). Arteriosclerosis in Parkinsonism. J. Neurol. Neurosurg. Psychiatry, 27, 237–240PubMedGoogle Scholar
  34. 34.
    Alvord, E. C. Jr. (1968). The pathology of Parkinsonism. In Minckler, J. (ed.) Pathology of the Nervous System. Vol. 1, pp. 1152–1161. (New York: McGraw-Hill)Google Scholar
  35. 35.
    Oppenheimer, D. R. (1976). Diseases of the basal ganglia, cerebellum and motor neurons. In Blackwood, W. and Corsellis, J. A. N. (eds.) Greenfield’s Neuropathology. 3rd Edn. pp. 608–651. (London: Arnold)Google Scholar
  36. 36.
    Bird, E. D. (1980). Chemical pathology of Huntington’s disease. Annu. Rev. Pharmacol Toxicol, 20, 533–551PubMedGoogle Scholar
  37. 37.
    Shoulson, I., Kartzinel, R. and Chase, T. N. (1976). Huntington’s disease: treatment with dipropylacetic acid and gamma-aminobutyric acid. Neurology, 26, 61–63PubMedGoogle Scholar
  38. 38.
    Perry, T. L., Wright, J. M., Hansen, S., Allan, B. M., Baird, P. A. and MacLeod, P. M. (1980). Failure of aminooxyacetic acid therapy in Huntington’s disease. Neurology, 30, 772–775PubMedGoogle Scholar
  39. 39.
    Manyam, B. V, Katz, L., Hare, T. A., Kaniefski, K. and Tremblay, R. D. (1981). Isoniazid-induced elevation of CSF GABA levels and effects on chorea in Huntington’s disease. Ann. Neurol, 10, 35–37PubMedGoogle Scholar
  40. 40.
    Butterfield, D. A., Oeswein, J. Q., Prunty, M. E., Hisle, K. C. and Markesbery, W. R. (1978). Increased sodium plus potassium adenosine triphosphatase activity in erythrocyte membranes in Huntington’s disease. Ann. Neurol, 4, 60–62PubMedGoogle Scholar
  41. 41.
    Mann, J. and Chiu, E. (1978). Platelet monoamine oxidase activity in Huntington’s chorea. J. Neurol, Neurosurg. Psychiatry, 41, 809–812Google Scholar
  42. 42.
    Ando, N., Gold, B. I., Bird, E. D. and Roth, R. H. (1979). Regional brain levels of γ-hydroxybutyrate in Huntington’s disease. J. Neurochem., 32, 617–622PubMedGoogle Scholar
  43. 43.
    Bird, E. D., Gale, J. S. and Spokes, E. G. (1977). Huntington’s chorea: postmortem activity of enzymes involved in cerebral glucose metabolism. J. Neurochem., 29, 539–545PubMedGoogle Scholar
  44. 44.
    Urquhart, N., Perry, T. L., Hansen, S. and Kennedy, J. (1975). GABA content and glutamic acid decarboxylase activity in brain of Huntington’s chorea patients and control subjects. J. Neurochem., 24, 1071–1075PubMedGoogle Scholar
  45. 45.
    Nausieda, P. A., Koller, W. C., Weiner, W. J. and Klawans, H. L. (1979). Chorea induced by oral contraceptives. Neurology, 29, 1605–1609PubMedGoogle Scholar
  46. 46.
    Dreese, M. J. and Netsky, M. G. (1968). Degenerative disorders of the basal ganglia. In Minckler, J. (ed.) Pathology of the Nervous System. Vol. 1, pp. 1185–1204. (New York: McGraw-Hill)Google Scholar
  47. 47.
    Corsellis, J. A. N. (1976). Ageing and the dementias. In Blackwood, W. and Corsellis, J. A. N. (eds.) Greenfield’s Neuropathology. 3rd Edn., pp. 796–848. (London: Arnold)Google Scholar
  48. 48.
    Martin, J. P. (1959). Remarks on the functions of the basal ganglia. Lancet, 1, 999–1005PubMedGoogle Scholar
  49. 49.
    Goetz, C. G., Weiner, W. J. and Klawans, H. L. (1981). Treatment of the choreas. In Barbeau, A. (ed.) Disorders of Movement, pp. 29–41. (Lancaster: MTP Press)Google Scholar
  50. 50.
    Baldessarini, R. J. and Tarsy, D. (1979). Relationship of the actions of neuroleptic drugs to the pathophysiology of tardive dyskinesia. Int. Rev. Neurobioi, 21, 1–45Google Scholar
  51. 51.
    Gerlach, J. (1979). Tardive dyskinesia. Danish Med. J., 46, 209–245Google Scholar
  52. 52.
    Snyder, S. H. (1979). Receptors, neurotransmitters and drug responses. N. Engl. J. Med., 300, 465–472PubMedGoogle Scholar
  53. 53.
    Weiss, B., Greenberg, L. and Cantor, E. (1979). Age-related alterations in the development of adrenergic denervation supersensitivity. Fed. Proc, 38, 1915–1921PubMedGoogle Scholar
  54. 54.
    Klawans, H. L. (1973). The Pharmacology of Extrapyramidal Movement Disorders. (Basel: Karger)Google Scholar
  55. 55.
    Creese, I. and Sibley, D. R. (1981). Receptor adaptations to centrally acting drugs. Annu. Rev. Pharmacol. Toxicol., 21, 357–391PubMedGoogle Scholar
  56. 56.
    Paulson, G. W. (1981). Treatment of tardive dyskinesia. In Barbeau, A. (ed.) Disorders of Movement, pp. 133–150. (Lancaster: MTP Press)Google Scholar
  57. 57.
    Wurtman, R. J., Hefti, F. and Melamed, E. (1981). Precursor control of neurotransmitter synthesis. Pharmacol. Rev., 32, 315–335Google Scholar
  58. 58.
    Eldridge, R., Kanter, W. and Koerber, T. (1973). Levodopa in dystonia. Lancet, 2, 1027–1028Google Scholar
  59. 59.
    Tolosa, E. S. (1981). Clinical features of Meige’s disease (idiopathic orofacial dystonia). A report of 17 cases. Arch. Neurol., 38, 147–151PubMedGoogle Scholar
  60. 60.
    Tolosa, E. S. and Lai, C. (1979). Meige disease: striatal dopaminergic preponderance. Neurology, 29, 1126–1130PubMedGoogle Scholar
  61. 61.
    Casey, D. E. (1980). Pharmacology of blepharospasm-oromandibular dystonia syndrome. Neurology, 30, 690–695PubMedGoogle Scholar
  62. 62.
    Snyder, S. H. (1981). Dopamine receptors, neuroleptics and schizophrenia. Am. J. Psychiatry, 138, 460–464PubMedGoogle Scholar
  63. 63.
    Bird, E. D., Spokes, E. G. S. and Iversen, L. I. (1980). Dopamine and noradrenaline in postmortem brain in Huntington’s disease and schizophrenic illness. Acta Psychiatr. Scand., 61 (Suppl. 280), 63–72Google Scholar
  64. 64.
    Fujita, K., Ito, T., Maruta, K., Teradaira, R., Beppu, H., Nakagami, Y., Kato, Y., Nagatsu, T. and Kato, T. (1978). Serum dopamine-γ-hydroxylase in schizophrenic patients. J. Neurochem., 30, 1569–1572PubMedGoogle Scholar
  65. 65.
    Leonard, B. E. (1975). Neurochemical and neuropharmacological aspects of depression. Int. Rev. Neurobioi, 18, 357–387Google Scholar
  66. 66.
    Maggi, A. and Enna, S. J. (1980). Regional alteration in rat brain neurotransmitter systems following chronic lithium treatment. J. Neurochem., 34, 888–892PubMedGoogle Scholar
  67. 67.
    Zis, A. P. and Goodwin, F. K. (1979). Novel antidepressants and the biogenic amine hypothesis of depression. The case for iprindole and mianserin. Arch. Gen. Psychiatry, 36, 1097–1107PubMedGoogle Scholar
  68. 68.
    Sandler, M., Ruthven, C. R. J., Goodwin, B. L., Reynolds, G. P., Rao, V. A. R. and Cohen, A. (1980). Trace amine deficit in depressive illness: the phenylalanine connexion. Acta Psychiatr. Scand., 61 (Suppl. 280), 29–38Google Scholar
  69. 69.
    Sulser, F., Vetulani, J. and Mobley, P. L. (1977). Mode of action of antidepressant drugs. Biochem. Pharmacol., 27, 257–261Google Scholar
  70. 70.
    Coppen, A. and Wood, K. M. (1980). Peripheral serotonergic and adrenergic responses in depression. Acta Psychiatr. Scand., 61 (Suppl. 280), 21–27Google Scholar
  71. 71.
    Herskovitz, E. and Blackwood, W. (1969). Essential (familial) tremor — a case report. J. Neurol., Neurosurg. Psychiatry, 32, 509–511Google Scholar
  72. 72.
    Murray, T. J. (1981). Essential tremor. In Barbeau, A. (ed.) Disorders of Movement, pp. 151–170. (Lancaster: MTP Press)Google Scholar
  73. 73.
    Van Praag, H. M. and De Haan, S. (1980). Central serotonin deficiency — a factor which increases depression vulnerability. Acta Psychiatr. Scand., 61 (Suppl. 280), 89–95Google Scholar
  74. 74.
    Gillin, J. C., Mendelson, W. B., Sitaram, N. and Wyatt, R. J. (1978). The neuropharmacology of sleep and wakefulness. Annu. Rev. Pharmacol. Toxicol., 18, 563–579PubMedGoogle Scholar
  75. 75.
    Wyler, A. R., Wilkus, R. J. and Troupin, A. S. (1975). Methysergide in the treatment of narcolepsy. Arch. Neurol., 32, 265–268PubMedGoogle Scholar
  76. 76.
    Growdon, J. H., Shahani, B. T. and Young, R. R. (1976). L-5-Hydroxytryptophan in treatment of several different syndromes in which myoclonus is prominent. Neurology, 26, 1135–1140PubMedGoogle Scholar
  77. 77.
    Magnussen, I., Dupont, E., Prange-Hansen, A. and De Fine Olivarius, B. (1977). Palatal myoclonus treated with 5-hydroxytryptophan and a decarboxylase inhibitor. Acta Neurol. Scand., 55, 251–253PubMedGoogle Scholar
  78. 78.
    Fennessy, M. R. and Lee, J. R. (1972). The effects of benzodiazepines on brain amines in the mouse. Arch. Intern. Pharmacodyn., 197, 37–44Google Scholar
  79. 79.
    Jenner, P., Chadwick, D., Reynolds, E. H. and Marsden, C. D. (1975). Altered 5HT metabolism with clonazepam, diazepam and diphenylhydantoin. J. Pharm. Pharmacol, 27, 707–710PubMedGoogle Scholar
  80. 80.
    Goldberg, M. A. and Dorman, J. D. (1976). Intention myoclonus successfully treated with clonazepam. Neurology, 26, 24–26Google Scholar
  81. 81.
    Lance, J. W. (1981). Headache. Ann. Neurol., 10, 1–10PubMedGoogle Scholar
  82. 82.
    Lance, J. W. (1978). Migraine. In Matthews, W. B. and Glaser, G. H. (eds.) Recent Advances in Clinical Neurology. Vol. 2, pp. 145–161. (Edinburgh: Churchill-Livingstone)Google Scholar
  83. 83.
    Bruyn, G. W. (1976). The biochemical basis of migraine: a critique. In Klawans, H. (ed.) Clinical Neuropharmacology. Vol. 1, pp. 185–213. (New York: Raven Press)Google Scholar
  84. 84.
    Hardebo, J. E., Edvinsson, L., Owman, C. H. and Svendgaard, N-Aa. (1978). Potentiation and antagonism of serotonin effects on intracranial and extracranial vessels. Neurology, 28, 64–70PubMedGoogle Scholar
  85. 85.
    Murphy, D. L. (1978). Substrate-selective monoamine oxidases-inhibitor, tissue, species and functional differences. Biochem. Pharmacol., 27, 1889–1893PubMedGoogle Scholar
  86. 86.
    Sandler, M., Reveley, M. A. and Glover, V. (1981). Human platelet monoamine oxidase activity in health and disease: a review. J. Clin. Pathol., 34, 292–302PubMedGoogle Scholar
  87. 87.
    Somerville, B. W. (1976). Platelet-bound and free serotonin levels in jugular and forearm venous blood during migraine. Neurology, 26, 41–45PubMedGoogle Scholar
  88. 88.
    Sicuteri, F. (1976). Migraine, a central biochemical dysnocioception. Headache, 16, 145–159PubMedGoogle Scholar
  89. 89.
    Anthony, M., Hinterberger, H. and Lance, J. W. (1967). Plasma serotonin in migraine and stress. Arch. Neurol., 16, 544–552PubMedGoogle Scholar
  90. 90.
    Regoli, D. and Barabe, J. (1980). Pharmacology of bradykinin and related kinins. Pharmacol Rev., 32, 1–46PubMedGoogle Scholar
  91. 91.
    Hanington, E. (1978). Migraine: a blood disorder. Lancet, 2, 501–502PubMedGoogle Scholar
  92. 92.
    Sandler, M., Youdim, M. B. H. and Hanington, E. (1974). A phenylethylamine oxidising defect in migraine. Nature (London), 250, 335–337PubMedGoogle Scholar
  93. 93.
    Glover, V., Sandler, M., Grant, E., Rose, F. C., Orton, D., Wilkinson, M. and Stevens, D. (1977). Transitory decrease in platelet monoamine-oxidase activity during migraine attacks. Lancet, 1, 391–393PubMedGoogle Scholar
  94. 94.
    Sandler, M. (1978). Implications of the platelet monoamine oxidase deficit during migraine attacks. Res. Clin. Stud. Headache, 6, 65–72PubMedGoogle Scholar
  95. 95.
    Masel, B. E., Chesson, A. L., Peters, B. H., Levin, H. S. and Alperin, J. B. (1980). Platelet antagonists in migraine prophylaxis. A clinical trial using aspirin and dipyridamole. Headache, 20, 13–18PubMedGoogle Scholar
  96. 96.
    Moncada, S. and Vane, J. R. (1979). Pharmacology and endogenous roles of prostaglandin endoperoxides, thromboxane A2, and prostacyclin. Pharmacol Rev., 30, 293–331Google Scholar
  97. 97.
    Sandler, M. (1972). Migraine: a pulmonary disease? Lancet, 1, 618–619PubMedGoogle Scholar
  98. 98.
    Neligan, P., Harriman, D. G. F. and Pearce, J. (1977). Respiratory arrest in familial hemiplegic migraine: a clinical and neuropathological study. Br. Med. J., 2, 732–734PubMedCentralPubMedGoogle Scholar
  99. 99.
    Raskin, N. H. (1981). Pharmacology of migraine. Annu. Rev. Pharmacol Toxicol, 21, 463–478PubMedGoogle Scholar
  100. 100.
    Symonds, C. P. (1956). A particular variety of headache. Brain, 79, 217–232PubMedGoogle Scholar
  101. 101.
    Anthony, M. and Lance, J. W. (1971). Whole blood histamine and plasma serotonin in cluster headache. Arch. Neurol, 25, 225–231PubMedGoogle Scholar
  102. 102.
    Andrews, P. R. and Johnston, G. A. R. (1979). GABA agonists and antagonists. Biochem. Pharmacol, 28, 2697–2702PubMedGoogle Scholar
  103. 103.
    Iversen, L. L. and Kelly, J. S. (1975). Uptake and metabolism of γ-aminobutyric acid by neurones and glial cells. Biochem. Pharmacol., 24, 933–938PubMedGoogle Scholar

Copyright information

© M. J. Eadie and J. H. Tyrer 1983

Authors and Affiliations

  • M. J. Eadie
    • 1
  • J. H. Tyrer
  1. 1.Department of MedicineUniversity of QueenslandBrisbaneAustralia

Personalised recommendations