Brain Dopamine: A Historical Perspective

  • O. Hornykiewicz
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 154 / 1)


To the student of the history of brain dopamine (DA), the amine offers an excellent example of an endogenous compound that right from the start has presented aspects of both scientific and clinical importance. Although on several points DA shares this characteristic with the other two catecholamines, adrenaline and noradrenaline (NA), what sets DA apart is the tightness of the interdigitation between its basic research and the clinical implications — for brain DA, there has never been a dividing line between the two; each has served as the driving force for the other. To bring out this interconnection has been the primary object of the following “Historical Perspective”. The decidedly human relevance of brain DA research also has been the ultimate vindication of the pleasure we take in our work as DA researchers. The writer has tried to convey in this essay some of the excitement of this work.


Basal Ganglion Historical Perspective Ergot Alkaloid Corpus Striatum Brain Dopamine 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Acheson GH (ed) (1966) Second Symposium on catecholamines, Pharmacol Rev, vol 18. Williams & Wilkins, BaltimoreGoogle Scholar
  2. Aghajanian GK, Bunney BS (1973) Central dopaminergic neurons: neurophysiological identification and responses to drugs. In: Usdin E, Snyder SH (eds) Frontiers in catecholamine research. Pergamon Press, New York Toronto Oxford Sydney Braunschweig, p 643Google Scholar
  3. Agid Y, Javoy F, Glowinski J (1973) Hyperactivity of remaining dopaminergic neurones after partial destruction of the nigro-striatal dopaminergic system in the rat. Nature 245:150–151Google Scholar
  4. Ahlquist RP (1948) A study of the adrenotropic receptors. Am J Physiol 153:586–600PubMedGoogle Scholar
  5. Anden N-E (1972) Dopamine turnover in the corpus striatum and the limbic System after treatment with neuroleptic and anti-acetylcholine drugs. J Pharm Pharmacol 24:905–906PubMedGoogle Scholar
  6. Andén N-E, Carlsson A, Dahlström A, Fuxe K, Hillarp N-A, Larsson K (1964a) Demonstration and mapping out of nigro-striatal dopamine neurons. Life Sei 3:523–530Google Scholar
  7. Andén N-E, Roos B-E, Werdinius B (1964b) Effects of chlorpromazine, haloperidol and reserpine on the levels of phenolic acids in rabbit corpus striatum. Life Sei 3:149–158Google Scholar
  8. Andén N-E, Dahlström A, Fuxe K, Larsson K, Olson L, Ungerstedt U (1966) Ascending monoamine neurons to the telencephalon and dieneephalon. Acta Physiol Scand 67:313–326Google Scholar
  9. Andén N-E, Rubenson A, Fuxe K, Hökfelt T (1967) Evidence for dopamine reeeptor Stimulation by apomorphine. J Pharm Pharmacol 19:627–629PubMedGoogle Scholar
  10. Andén N-E, Butcher SG, Corrodi H, Fuxe K, Ungerstedt U (1970) Reeeptor activity and turnover of dopamine and noradrenaline after neuroleptics. Eur J Pharmacol 11:303–314PubMedGoogle Scholar
  11. Ballard PA, Tetrud JW, Langston JW (1985) Permanent human parkinsonism due to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): seven cases. Neurology 35:949–956PubMedGoogle Scholar
  12. Barbeau A (1962) The pathogenesis of Parkinson’s disease: a new hypothesis. Can Med Ass J 87:802–807PubMedGoogle Scholar
  13. Barbeau A (1969) L-Dopa therapy in Parkinson’s disease: a critical review of nine years’ experience. Can Med Ass J 101:791–800Google Scholar
  14. Barbeau A, Murphy GF, Sourkes TL (1961) Excretion of dopamine in diseases of basal ganglia. Science 133:1706–1707PubMedGoogle Scholar
  15. Barbeau A, Sourkes TL, Murphy GF (1962) Les catécholamines dans la maladie de Parkinson. In: de Ajuriaguerra J (ed) Monoamines et Systeme nerveux centrale. Georg, Genève and Masson, Paris, p 247Google Scholar
  16. Barger G, Dale HH (1910) Chemical structure and sympathomimetic action of amines. J Physiol 41:19–59PubMedGoogle Scholar
  17. Barger G, Ewins AJ (1910) Some phenolic derivatives of ß-phenylethylamine. J Chem Soc (London) 97:2253–2261Google Scholar
  18. Barolin GS, Bernheimer H, Hornykiewicz O (1964) Seitenverschiedenes Verhalten des Dopamins (3-Hydroxytyramin) im Gehirn eines Falles von Hemi-parkinsonismus. Schweiz Arch Neurol Psychiat 94:241–248Google Scholar
  19. Bernheimer H, Hornykiewicz O (1965) Herabgesetzte Konzentration der Homovanillinsäure im Gehirn von parkinsonkranken Menschen als Ausdruck der Störung des zentralen Dopaminstoffwechsels. Klin Wschr 43:711–715PubMedGoogle Scholar
  20. Bernheimer H, Hornykiewicz O (1973) Brain amines in Huntington’s chorea. Adv Neurol 1:525–531Google Scholar
  21. Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seiteiberger F (1973) Brain dopamine and the Syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J Neurol Sci 20:415–455PubMedGoogle Scholar
  22. Bertler å (1961) Occurrence and localization of catecholamines in the human brain. Acta Physiol Scand 51:97–107Google Scholar
  23. Bertler å, Rosengren E (1959) Occurrence and distribution of dopamine in brain and other tissues. Experientia 15:10–11PubMedGoogle Scholar
  24. Bertler å, Rosengren E (1966) Possible role of brain dopamine. Pharmacol Rev 18:769–773PubMedGoogle Scholar
  25. Bing RJ (1941) The formation of hydroxytyramine by extracts of renal cortex and by perfused kidneys. Am J Physiol 132:497–503Google Scholar
  26. Bing RJ, Zucker MB (1941) Renal hypertension produced by an amino acid. J Exp Med 74:235–245PubMedGoogle Scholar
  27. Birkmayer W, Hornykiewicz O (1961) Der L-Dioxyphenylalanin (= DOPA)-Effekt bei der Parkinson-Akinese. Wien Klin Wschr 73:787–788PubMedGoogle Scholar
  28. Birkmayer W, Hornykiewicz O (1962) Der L-Dioxyphenylalanin (= DOPA)-Effekt beim Parkinson-Syndrom des Menschen: zur Pathogenese und Behandlung der Parkinson-Akinese. Arch Psychiat Nervenkr 203:560–574PubMedGoogle Scholar
  29. Björklund A, Stenevi U (1979) Reconstruction of the nigrostriatal dopamine pathway by intracerebral nigral transplants. Brain Res 177:555–560PubMedGoogle Scholar
  30. Blaschko H (1939) The specific action of L-dopa decarboxylase. J Physiol 96:50P-51PGoogle Scholar
  31. Blaschko H (1952) Amine oxidase and amine metabolism. Pharmacol Rev 4:415–458PubMedGoogle Scholar
  32. Blaschko H (1957) Metabolism and storage of biogenic amines. Experientia 13:9–12PubMedGoogle Scholar
  33. Blaschko H, Chrusciel TL (1960) The decarboxylation of amino acids related to tyrosine and their awakening action in reserpine-treated mice. J Physiol 151:272–284PubMedGoogle Scholar
  34. Bloom FE, Costa E, Salmoiraghi GC (1965) Anesthesia and the responsiveness of individual neurons of the caudate nucleus of the cat to acetylcholine, norepinephrine and dopamine administration by microelectrophoresis. J Pharmacol Exp Ther 150:244–252PubMedGoogle Scholar
  35. Brodie BB, Costa E (1962) Some current views on brain monoamines. In: de Ajuriaguerra J (ed) Monoamines et Systeme nerveux central. Georg, Genève and Masson, Paris, p 13Google Scholar
  36. Brozoski TJ, Brown RM, Ptak J, Goldman PS (1979) Dopamine in prefrontal cortex of rhesus monkeys: evidence for a role in cognitive funetion. In: Usdin E, Kopin IJ, Barchas J (eds) Catecholamines: basic and clinical frontiers, vol 2. Pergamon Press, New York Oxford, p 1681Google Scholar
  37. Calne DB, Teychenne PF, Claveria LE, Eastman R, Greenacre JK, Petrie A (1974) Bromocriptine in parkinsonism. Brit Med J 4:442–444PubMedGoogle Scholar
  38. Carlsson A (1959) The occurrence, distribution and physiological role of catecholamines in the nervous System. Pharmacol Rev 11:490–493PubMedGoogle Scholar
  39. Carlsson A (1964) Functional significance of drug-induced changes in brain monoamine levels. In: Himwich HE, Himwich WA (eds) Progr Brain Res 8: Biogenic amines. Elsevier, Amsterdam, p 9Google Scholar
  40. Carlsson A (1965) Drugs which block the storage of 5-hydroxytryptamine and related amines. In: Eichler O, Farah A (eds) 5-Hydroxytryptamine and related indolealkylamines. Springer, Berlin Heidelberg New York (Handbook of Experimental Pharmacology, vol 19) pp 529–592)Google Scholar
  41. Carlsson A, Lindqvist M, Magnusson T (1957) 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists. Nature 180:1200PubMedGoogle Scholar
  42. Carlsson A, Lindqvist M, Magnusson T, Waldeck B (1958) On the presence of 3-hydroxytyramine in brain. Science 127:471PubMedGoogle Scholar
  43. Carlsson A, Lindqvist M (1962) DOPA analogues as tools for the study of dopamine and noradrenaline in brain. In: de Ajuriaguerra J (ed) Monoamines et système nerveux central. Georg, Genève and Masson, Paris, p 89Google Scholar
  44. Carlsson A, Lindqvist M (1963) Effect of chlorpromazine or haloperidol on formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta Pharm Tox 20:140–144PubMedGoogle Scholar
  45. Clouet DH, Ratner RL (1970) Catecholamine biosynthesis in brains of rats treated with morphine. Science 168:854–855PubMedGoogle Scholar
  46. Connor JD (1970) Caudate nucleus neurones: correlation of the effects of substantia nigra Stimulation with iontophoretic dopamine. J Physiol 208:691–703PubMedGoogle Scholar
  47. Corrodi H, Fuxe K, Hökfelt T, Lidbrink P, Ungerstedt U (1973) Effect of ergot drugs on central catecholamine neurons: evidence for a Stimulation of central dopamine neurons. J Pharm Pharmacol 25:409–411PubMedGoogle Scholar
  48. Costa E, Côté LJ, Yahr MD (eds) (1966) Biochemistry and pharmacology of the basal ganglia. Raven Press, Hewlett, New YorkGoogle Scholar
  49. Cotzias GC, Van Woert MH, Schiffer IM (1967) Aromatic amino acids and modification of Parkinsonism. New Engl J Med 276:374–379PubMedGoogle Scholar
  50. Coyle JT, Snyder SH (1969a) Catecholamine uptake by synaptosomes in homogenates of rat brain: stereospecificity in different areas. J Pharmacol Exp Ther 170:221–231PubMedGoogle Scholar
  51. Coyle JT, Snyder SH (1969b) Antiparkinsonian drugs: inhibition of dopamine uptake in the corpus striatum as a possible mechanism of action. Science 166:899–901PubMedGoogle Scholar
  52. Creese I, Burt DR, Snyder SH (1975) Dopamine reeeptor binding: differentiation of agonist and antagonist states with 3H-dopamine and 3H-haloperidol. Life Sci 17:993–1002Google Scholar
  53. Creese I, Burt DR, Snyder SH (1976) Dopamine reeeptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 192:481–483PubMedGoogle Scholar
  54. Curtis DR, Davis R (1961) A central action of 5-hydroxytryptamine and noradrenaline. Nature 192:1083–1084PubMedGoogle Scholar
  55. Dahlström A, Fuxe K (1964) Evidence for the existence of monoamine-containing neurons in the central nervous System. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol Scand 62:suppl 232Google Scholar
  56. Dale H (1943) Modes of drug action. General introduetory address. Trans Faraday Soc 39:319–322Google Scholar
  57. Degkwitz R, Frowein R, Kulenkampff C, Mohs U (1960) über die Wirkungen des L-DOPA beim Menschen und deren Beeinflussung durch Reserpin, Chlorpromazin, Iproniazid and Vitamin B6. Klin Wschr 38:120–123PubMedGoogle Scholar
  58. DeLong MR, Georgopoulos AP, Crutcher MD (1983) Cortico-basal ganglia relations and coding of motor Performance. Exp Brain Res (Suppl) 7:30–39Google Scholar
  59. DeLong MR (1990) Primate models of movement disorders of basal ganglia origin. Trends Neurosci 13:281–285PubMedGoogle Scholar
  60. Denny-Brown D (1966) The Cerebral Control of Movement (Sherrington lectures for 1963). Liverpool University Press, Liverpool.Google Scholar
  61. DiChiara G, Imperato A (1988) Drugs abused by humans preferentially increase synaptic dopamine concentration in the mesolimbic System of freely moving rats. Proc Natl Acad Sci USA 85:5274–5278Google Scholar
  62. DiChiara G, Morelli M, Consolo S (1994) Modulatory funetions of neurotransmitters in the striatum: ACh/dopamine/NMDA interactions. Trends Neurosci 17:228–233Google Scholar
  63. Eble JN (1964) A proposed mechanism for the depressor effect of dopamine in the anesthetized dog. J Pharmacol Exp Ther 145:64–70PubMedGoogle Scholar
  64. Ehringer H, Hornykiewicz O (1960) Verteilung von Noradrenalin und Dopamin (3-Hydroxytyramin) im Gehirn des Menschen und ihr Verhalten bei Erkrankungen des extrapyramidalen Systems. Klin Wschr 38:1236–1239PubMedGoogle Scholar
  65. Ernst AM (1965) Relation between the action of dopamine and apomorphine and their O-methylated derivatives upon the CNS. Psychopharmacologia 7:391–399PubMedGoogle Scholar
  66. Ernst AM (1967) Mode of action of apomorphine and dexamphetamine on gnawing compulsion in rats. Psychopharmacologia 10:316–323PubMedGoogle Scholar
  67. Ernst AM, Smelik PG (1966) Site of action of dopamine and apomorphine on compulsive gnawing behaviour in rats. Experientia 22:837PubMedGoogle Scholar
  68. Evarts EV, Kimura M, Wurtz RH, Hikosaka O (1984) Behavioural correlates of activity in basal ganglia neurons. Trends Neurosci 7:447–453Google Scholar
  69. Everett GM (1961) Some electrophysiological and biochemical correlates of motor activity and aggressive behavior. Neuro-Psychopharmacol 2:479–484Google Scholar
  70. Everett GM (1970) Evidence for dopamine as a central neuromodulator: neurological and behavioral implications. In: Barbeau A, McDowell FH (eds) L-DOPA and Parkinsonism. FA Davis, Philadelphia, p. 364Google Scholar
  71. Everett GM, Toman JEP (1959) Mode of action of Rauwolfia alkaloids and motor activity. Biol Psychiat 2:75–81Google Scholar
  72. Everett GM, Wiegand RG (1962) Central amines and behavioral states: a critique and new data. Proc. 1st Internat Pharmacol Meeting 8:85–92Google Scholar
  73. Flückiger E, Wagner HR (1968) 2-Br-a-Ergokryptin: Beeinflussung von Fertilität und Laktation bei der Ratte. Experientia 24:1130PubMedGoogle Scholar
  74. Funk C (1911) Synthesis of dl-3:4-dihydroxyphenylalanine. J Chem Soc 99:554–557Google Scholar
  75. Fuxe K (1964) Cellular localization of monoamines in the median eminence and the infundibular stem of some mammals. Z Zellforsch 61:710–724PubMedGoogle Scholar
  76. Fuxe K (1965) Evidence for the existence of monoamine neurons in the central nervous system. IV. Distribution of monoamine nerve terminals in the central nervous system. Acta Physiol Scand 64:Suppl 247Google Scholar
  77. Fuxe K, Hökfelt T (1970) Central monoaminergic systems and hypothalamic funetion. In: Martini L, Motta M, Fraschini F (eds) The hypothalamus. Academic Press, New York, p 123Google Scholar
  78. Gage FH, Kawaja MD, Fisher LJ (1991) Genetically modified cells: applications for intracerebral grafting. Trends Neurosci 14:328–333PubMedGoogle Scholar
  79. Gerstenbrand F, Pateisky K, Prosenz P (1963) Erfahrungen mit L-Dopa in der Therapie des Parkinsonismus. Psychiat Neurol 146:246–261Google Scholar
  80. Giros B, Jaber M, Jones SR, Wightman RM, Caron MG (1996) Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature 379:606–612PubMedGoogle Scholar
  81. Glowinski J, Iversen L (1966) Regional studies of catecholamines in the rat brain — III: subcellular distribution of endogenous and exogenous catecholamines in various brain regions. Biochem Pharmacol 15:977–987PubMedGoogle Scholar
  82. Glowinski J, Cheramy A, Giorguieff MF (1979) In-vivo and in-vitro release of dopamine. In: Horn AS, Korf J, Westerink BHC (eds) The neurobiology of dopamine. Academic Press, London New York San Francisco, p 199Google Scholar
  83. Goldberg LI (1972) Cardiovascular and renal actions of dopamine: potential clinical applications. Pharmacol Rev 24:1–29PubMedGoogle Scholar
  84. Goldstein M, Anagnoste B, Owen WS, Battista AF (1966) The effects of ventromedial tegmental lesions on the biosynthesis of catecholamines in the striatum. Life Sci 5:2171–2176Google Scholar
  85. Goodall McC (1951) Studies of adrenaline and noradrenaline in mammalian hearts and suprarenals. Acta Physiol Scand 24: Suppl 85Google Scholar
  86. Graybiel AM, Ragsdale Jr CW (1979) Fiber connections of the basal ganglia. Progr Brain Res 51:239–283Google Scholar
  87. Guggenheim M (1913) Dioxyphenylalanin, eine neue Aminosäure aus vicia faba. Z Physiol Chem 88:276–284Google Scholar
  88. Hasama B-I (1930) Beiträge zur Erforschung der Bedeutung der chemischen Konfiguration für die pharmakologischen Wirkungen der adrenalinähnlichen Stoffe. Arch Exp Path Pharmakol 153:161–186Google Scholar
  89. Hassler R (1938) Zur Pathologie der Paralysis agitans und des postenzephalitischen Parkinsonismus. J Psychol Neurol 48:387–476Google Scholar
  90. Hertting G, Axelrod J (1961) Fate of tritiated noradrenaline at the sympathetic nerve endings. Nature 192:172–173PubMedGoogle Scholar
  91. Hertting G, Axelrod J, Kopin IJ, Whitby LG (1961) Lack of uptake of catecholamines after chronic denervation of sympathetic nerves. Nature 189:66PubMedGoogle Scholar
  92. Himwich HE, Himwich WA (eds) (1964) Progress Brain Res 8: Biogenic amines. Elsevier, AmsterdamGoogle Scholar
  93. Hökfelt T, Fuxe K (1972) Effects of prolactin and ergot alkaloids on the tuberoinfundibular dopamine (DA) neurons. Neuroendocrinology 9:100–122PubMedGoogle Scholar
  94. Holtz P (1939) Dopadecarboxylase. Naturwissenschaften 27:724–725Google Scholar
  95. Holtz P, Heise R, Lüdtke K (1938) Fermentativer Abbau von 1-Dioxyphenylalanin durch die Niere. Arch Exp Path Pharmak 191:87–118Google Scholar
  96. Holtz P, Credner K (1942) Die enzymatische Entstehung von Oxytyramin im Organismus und die physiologische Bedeutung der Dopadecarboxylase. Arch Exp Path Pharmak 200:356–388Google Scholar
  97. Hornykiewicz O (1958) The action of dopamine on the arterial pressure of the guinea pig. Brit J Pharmacol 13:91–94PubMedGoogle Scholar
  98. Hornykiewicz O (1963) Die topische Lokalisation und das Verhalten von Noradrenalin und Dopamin (3-Hydroxytyramin) in der Substantia nigra des normalen und Parkinsonkranken Menschen. Wien Klin Wschr 75:309–312PubMedGoogle Scholar
  99. Hornykiewicz O (1964) Zur Frage des Verlaufs dopaminerger Neurone im Gehirn des Menschen. Wien Klin Wschr 76:834–835PubMedGoogle Scholar
  100. Hornykiewicz O (1966) Dopamine (3-hydroxytyramine) and brain function. Pharmacol Rev 18:925–964PubMedGoogle Scholar
  101. Hornykiewicz O (1976) Neurohumoral interactions and basal ganglia function and dysfunction. In: Yahr MD (ed) The basal ganglia. Raven Press, New York, p 269Google Scholar
  102. Hornykiewicz O (1978) Psychopharmacological implications of dopamine and dopamine antagonists: a critical evaluation of current evidence. Neuroscience 3:773–783PubMedGoogle Scholar
  103. Hornykiewicz O (1986) A quarter Century of brain dopamine research. In: Woodruff GN, Poat JA, Roberts PJ (eds) Dopaminergic Systems and their regulation. Macmillan, London, p 3Google Scholar
  104. Hornykiewicz O (1992) From dopamine to Parkinson’s disease: a personal research record. In: Samson F, Adelman G (eds) The neurosciences: paths of discovery II. Birkhäuser, Boston, p 125Google Scholar
  105. Hornykiewicz O (1994) Levodopa in the 1960s: starting point Vienna. In: Poewe W, Lees AJ (eds) 20 Years of madopar - new avenues. Editiones Roche, Basel, p 11Google Scholar
  106. Hornykiewicz O (1998) Biochemical aspects of Parkinson’s disease. Neurology 51: Suppl 2: S2-S9Google Scholar
  107. Hornykiewicz O (2001) How L-DOPA was discovered as a drug for Parkinson’s disease 40 years ago. Wien Klin Wschr 113:855–862PubMedGoogle Scholar
  108. Iversen LL (1975) Uptake processes for biogenic amines. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology, vol 3: Biochemistry of biogenic amines. Plenum Press, New York, London, p 381Google Scholar
  109. Jenner P (1998) Oxidative mechanisms in nigral cell death in Parkinson’s disease. Movement Disorders 13:24–34PubMedGoogle Scholar
  110. Jonsson G (1980) Chemical neurotoxins as denervation tools in neurobiology. Ann Rev Neurosci 3:169–187PubMedGoogle Scholar
  111. Jonsson G, Malmfors T, Sachs Ch (eds) (1975) Chemical tools in catecholamine research I. 6-Hydroxydopamine as a denervation tool in catecholamine research. North Holland, AmsterdamGoogle Scholar
  112. Kebabian JW, Petzold GL, Greengard P (1972) Dopamine-sensitive adenylate cyclase in caudate nucleus of rat brain, and its similarity to the “dopamine reeeptor”. Proc Natl Acad Sci 69:2145–2149PubMedGoogle Scholar
  113. Kebabian JW, Calne DB (1979) Multiple reeeptors for dopamine. Nature 277:93–96PubMedGoogle Scholar
  114. Kehr W, Carlsson A, Lindqvist M, Magnusson T, Attack C (1972) Evidence for a reeeptor-mediated feedback control of striatal tyrosine hydroxylase activity. J Pharm Pharmacol 24:744–747PubMedGoogle Scholar
  115. Kerkut GA, Walker RJ (1961) The effects of drugs on the neurons of the snail Helix aspersa. Comp Biochem Physiol 3:143–160PubMedGoogle Scholar
  116. Kerkut GA, Walker RJ (1962) The specific chemical sensitivity of Helix nerve cells. Comp Biochem Physiol 7:277–288PubMedGoogle Scholar
  117. Kuschinsky K, Hornykiewicz O (1972) Morphine catalepsy in the rat: relation to striatal dopamine metabolism. Eur J Pharmacol 19:119–122PubMedGoogle Scholar
  118. Langston JW, Ballard PA, Tetrud JW, Irwin I (1983) Chronic parkinsonism in humans due to a produet of meperidine-analog synthesis. Science 219:979–980PubMedGoogle Scholar
  119. Langston JW, Irwin I (1986) MPTP: current coneepts and controversies. Clin Neuropharmacol 9:485–507PubMedGoogle Scholar
  120. Laverty R (1974) On the roles of dopamine and noradrenaline in animal behaviour. Progr Neurobiol 3:31–70Google Scholar
  121. Lee T, Seeman P, Rajput A, Farley IJ, Hornykiewicz O (1978) Reeeptor basis for dopaminergic supersensitivity in Parkinson’s disease. Nature 273:59–61PubMedGoogle Scholar
  122. Levant B, Ling ZD, Carvey PM (1999) Dopamine D3 receptors. Relevance for the drug treatment of Parkinson’s disease. CNS Drugs 12:391–402Google Scholar
  123. Lloyd KG (1977) Neurotransmitter interactions related to central dopamine neurons. In: Youdim MBH, Lovenberg W, Sharman DF, Lagnado TR (eds) Essays in neurochemistry and neuropharmacology. John Wiley & Sons, Chichester, p 131Google Scholar
  124. Mannich C, Jacobsohn W (1910) über Oxyphenylalkylamine und Dioxyphenylalkylamine. Ber Deut Chem Ges 43:189–197Google Scholar
  125. Markey SP, Castagnoli Jr N, Trevor AJ, Kopin IJ (eds) (1986) MPTP: a neurotoxin producing a parkinsonian syndrome. Academic Press, Orlando.Google Scholar
  126. McGeer EG, McGeer PL, McLennan H (1961a) The inhibitory action of 3-hydroxytyramine, gamma-aminobutyric acid (GABA) and some other Compounds towards the crayfish Stretch reeeptor neuron. J Neurochem 8:36–49Google Scholar
  127. McGeer PL, Boulding JE, Gibson WC, Foulkes RG (1961b) Drug-induced extrapyramidal reactions. JAMA 177:665–670PubMedGoogle Scholar
  128. Milhaud G, Glowinski J (1962) Métabolism de la dopamine-14C dans le cerveau du Rat. ètude du mode d’administration. CR Acad Sci (Paris) 255:203–205Google Scholar
  129. Miller GW, Gainetdinov RR, Levey AI, Caron MG (1999) Dopamine transporters and neuronal injury. Trends Pharmacol Sci 20:424–429PubMedGoogle Scholar
  130. McLennan H, York DH (1967) The action of dopamine on neurones of the caudate nucleus. J Physiol 189:393–402PubMedGoogle Scholar
  131. Montagu KA (1957) Catechol Compounds in rat tissues and in brains of different animals. Nature 180:244–245PubMedGoogle Scholar
  132. Moore RY (1970) The nigrostriatal pathway: demonstration by anterograde degeneration. In: Barbeau A, McDowell FH (eds) L-DOPA and parkinsonism. FA Davis Company, Philadelphia, p 143Google Scholar
  133. Narabayashi H (1990) Surgical treatment in the levodopa era. In: Stern G (ed) Parkinson’s disease. Chapman & Hall, London, p 597Google Scholar
  134. Parent A, Hazrati L-N (1995) Functional anatomy of the basal ganglia I. The corticobasal ganglia-thalamo-cortical loop. Brain Res Rev 20:91–127PubMedGoogle Scholar
  135. Pijnenburg AJJ, van Rossum JM (1973) Stimulation of locomotor activity following injection of dopamine into the nucleus accumbens. J Pharm Pharmacol 25:1003–1005PubMedGoogle Scholar
  136. Pletscher A, DaPrada M (1993) Pharmacotherapy of Parkinson’s disease: research from 1960 to 1991. Acta Neurol Scand 87: Suppl 146:26–31Google Scholar
  137. Poirier LJ, Sourkes TL (1965) Influence of the substantia nigra on the catecholamine content of the striatum. Brain 88:181–192PubMedGoogle Scholar
  138. Randrup A, Munkvad I (1972) Evidence indicating an association between schizophrenia and dopaminergic hyperactivity in the brain. Orthomolec Psychiat 1:2–7Google Scholar
  139. Sano I (1960) Biochemistry of the extrapyramidal system. Shinkei Kennkyu No Shinpo 5:42–48 (First tranlation from the original Japanese in: Parkinsonism Relat Disord (2000) 6:3–6Google Scholar
  140. Sano I, Gamo T, Kakimoto Y, Taniguchi K, Takesada M, Nishinuma K (1959) Distribution of catechol Compounds in human brain. Biochim Biophys Acta 32:586–587PubMedGoogle Scholar
  141. Sasame HA, Perez-Cruet J, DiChiara G, Tagliamonte A, Tagliamonte P, Gessa GL (1972) Evidence that methadone blocks dopamine reeeptors in the brain. J Neurochem 19:1953–1957PubMedGoogle Scholar
  142. Schwab RS, Amador LV, Lettvin JY (1951) Apomorphine in Parkinson’s disease. Trans Amer Neurol Ass 76:251–253Google Scholar
  143. Schwartz J-C, Giros B, Martres M-P, Sokoloff P (1993) Multiple dopamine reeeptors as molecular targets for antipsychotics. In: Brunello N, Mendlewicz J, Racagni G (eds) New generation of antipsychotic drugs: novel mechanisms of action. Int Acad Biomed Drug Res, vol 4. Karger, Basel, p 1Google Scholar
  144. Seeman P (1980) Brain dopamine reeeptors. Pharmacol Rev 32:229–313PubMedGoogle Scholar
  145. Seeman P, Chau-Wong M, Tedesco J, Wong K (1975) Brain reeeptors for antipsychotic drugs and dopamine: direct binding assays. Proc Natl Acad Sci USA 72:4376–4380PubMedGoogle Scholar
  146. Senoh S, Creveling CR, Udenfriend S, Witkop B (1959) Chemical, enzymatic and metabolic studies on the mechanism of oxidation of dopamine. J Am Chem Soc 81:6236–6240Google Scholar
  147. Snyder SH (1973) Amphetamine psychosis: a model schizophrenia mediated by catecholamines. Am J Psychiat 130:61–67PubMedGoogle Scholar
  148. Sokoloff P, Schwartz J-C (1995) Novel dopamine reeeptors half a decade later. Trends Pharmacol Sci 16:270–275PubMedGoogle Scholar
  149. Solomon P, Mitchell R, Prinzmetal M (1937) The use of benzedrine sulfate in postencephalitic Parkinson’s disease. JAMA 108:1765–1770Google Scholar
  150. Sourkes TL (2000) How dopamine was recognised as a neurotransmitter: a personal view. Parkinsonism Relat Disord 6:63–67PubMedGoogle Scholar
  151. Sourkes TL, Poirier L (1965) Influence of the substantia nigra on the concentration of 5-hydroxytryptamine and dopamine of the striatum. Nature 207:202–203PubMedGoogle Scholar
  152. Spano PF, Govoni S, Trabucchi M (1978) Studies on the pharmacological properties of dopamine reeeptors in various areas of the central nervous System. Adv Biochem Psychopharmacol 19:155–165PubMedGoogle Scholar
  153. Tanda G, Pontieri FE, DiChiara G (1997) Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common μ1 Opioid reeeptor mechanism. Science 276:2048–2050PubMedGoogle Scholar
  154. Trabucchi E, Paoletti R, Canal N, Volicer L (eds) (1964) Biochemical and neurophysiological correlation of centrally acting drugs. Pergamon Press, OxfordGoogle Scholar
  155. Ungerstedt U (1968) 6-Hydroxydopamine induced degeneration of central monoamine neurons. Eur J Pharmacol 5:107–110PubMedGoogle Scholar
  156. Ungerstedt U (1979) Central dopamine mechanisms and unconditioned behaviour. In: Horn AS, Korf J, Westerink BHC (eds) The neurobiology of dopamine. Academic Press, London New York San Francisco, p 577Google Scholar
  157. Ungerstedt U, Avemo A, Avemo E, Ljungberg T, Ranje C (1973) Animal models of parkinsonism. Adv Neurol 3:257–271Google Scholar
  158. Usdin E, Bunney Jr WE (eds) (1975) Pre- and postsynaptic reeeptors. Marcel Dekker Inc, New YorkGoogle Scholar
  159. Vane JR, Wolstenholme GEW, O’Connor M (eds) (1960) Adrenergic mechanisms, Ciba Foundation Symposium. Churchill, LondonGoogle Scholar
  160. van Rossum JM (1964) Significance of dopamine in psychomotor stimulant action. In: Trabucchi E, Paoletti R, Canal N, Volicer L (eds) Biochemical and neurophysiological correlation of centrally acting drugs. Pergamon Press, Oxford, p 115Google Scholar
  161. van Rossum JM (1965) Different types of sympathomimetic α-receptors. J Pharm Pharmacol 17:202–216Google Scholar
  162. van Rossum JM (1966) The significance of dopamine-receptor blockade for the action of neuroleptic drugs. Excerpta Med Intern Congr Series, no 129:321–329Google Scholar
  163. van Rossum JM, Hurkmans JAThM (1964) Mechanism of action of psychomotor stimulant drugs. Significance of dopamine in locomotor stimulant action. Int J Neuropharmacol 3:227–239Google Scholar
  164. Vogt M (1954) The concentration of sympathin in different parts of the central nervous System under normal condition and after the administration of drugs. J Physiol 123:451–481PubMedGoogle Scholar
  165. Wichmann T, DeLong MR (1996) Functional and pathophysiological models of the basal ganglia. Curr Opin Neurobiol 6:751–758PubMedGoogle Scholar
  166. Zigmond MJ, Stricker EM (1989) Animal models of parkinsonism using selective neurotoxins. Int Rev Neurobiol 31:1–79PubMedGoogle Scholar
  167. Zigmond MJ, Abercrombie ED, Berger TW, Grace AA, Stricker EM (1990) Compensations after lesions of central dopaminergic neurons: some clinical and basic implications. Trends Neurosci 13:290–296PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2002

Authors and Affiliations

  • O. Hornykiewicz

There are no affiliations available

Personalised recommendations