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Pharmakologie der Neuroleptika und relevante Mechanismen zur Behandlung von Minussymptomatik

  • C. J. E. Niemegeers
  • F. Awouters
  • P. A. J. Janssen

Zusammenfassung

Neuroleptika sind zu Standardarzneimitteln in der Behandlung der Schizophrenie geworden. Als pharmakologische Klasse weisen alle bekannten Neuroleptika eine gemeinsame Eigenschaft auf: den zentralen Dopaminantagonismus. Die beobachteten klinischen Unterschiede zwischen den einzelnen Neuroleptika wurden zeitweise spezifischen Wechselwirkungen mit Dopamin-rezeptorsubtypen oder mit Dopaminrezeptoren in besonderen Hirnarealen zugeschrieben. Wechselwirkungen mit anderen Neurotransmittern als Dopamin könnten ebenfalls eine Ursache der signifikanten klinischen Unterschiede sein. Neuere Untersuchungen haben bewiesen, daß der Serotoninantagonismus die antipsychotische Wirkung der Dopaminantagonisten unterstützt. Die experimentellen und klinischen Grundlagen der Dopamin- und der Serotoninhypothese werden im weiteren besprochen.

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Literatur

  1. Ansoms C, De Backer-Dierick C, Vereecken JLTM (1977) Sleep disorders in patients with severe mental depression. Double-blind placebo controlled evaluation of the value of pipamperone (Dipiperon). Acta Psychiatr Scand 55: 116–122.PubMedCrossRefGoogle Scholar
  2. Awouters F, Niemegeers CJE, Megens AAHP, Meert TF, Janssen PAJ (1988) The pharmacological profile of ritanserin, a very specific central serotonin S2 antagonist. Drug Dev Res 15: 61–73.CrossRefGoogle Scholar
  3. Balsara JJ, Jadhav JH, Chandorkar AG (1979) Effects of drugs influencing central serotonergic mechanisms on haloperidol-induced catalepsy. Psychopharmacology 62: 67–69.PubMedCrossRefGoogle Scholar
  4. Bersani G, Bressa GM, Meco G, Marini S, Pozzi F (1990) Combined serotonin 5HT2 and dopamine D2 antagonism in schizophrenia: clinical, extrapyramidal and neuroendocrine response in a preliminary study with risperidone (R 64766). Human Psychopharmacology 5: 225–231.CrossRefGoogle Scholar
  5. Bersani G, Grispini A, Marini S, Pasini A, Valducci M, Ciani N (1986) Neuroleptic-induced extrapyramidal side effects: clinical perspectives with ritanserin (R 55667), a new selective 5-HT2 receptor blocking agent. Curr Ther Res 40: 492–499.Google Scholar
  6. Carlsson A (1975) Dopaminergic autoreceptors. In: Almgren O, Carlsson A, Engel J (eds) Chemical tools in catecholamine research, Vol II. North Holland, Amsterdam, pp 219–224.Google Scholar
  7. Carter CJ, Pycock CJ (1977) Possible importance of 5-hydroxytryptamine in neuroleptic-induced catalepsy in rats. Br J Pharmacol 60: 267–268.Google Scholar
  8. Castelao JF, Ferreira L, Gelders YG, Heylen SLE (1989) The efficacy of the D2 and 5HT2 antagonist risperidone (R 55667) in the treatment of chronic psychosis. An open dosefinding study. Schizophr Res 2: 411–415.PubMedCrossRefGoogle Scholar
  9. Cerletti A, Doepfner W (1958) Spezifische Steigerung der serotoninantagonistischen Wirkung von Lysergsäurederivaten durch Methylierung des Indolstickstoffes der Lysergsäure. Helv Physiol Pharmacol Acta 16: C55–C57.Google Scholar
  10. Ceulemans DLS, Hoppenbrouwers M-LJA, Gelders YG, Reyntjens AJM (1985) The influence of ritanserin, a serotonin antagonist, in anxiety disorders; a double-blind placebo-controlled study versus lorazepam. Pharmacopsychiatry 18: 303–305.PubMedCrossRefGoogle Scholar
  11. Chang WH, Chen TY, Wu HS, Hu WH, Yeh EK (1988) Dose response curves of homovanillic acid in pre-frontal cortex and caudate following antipsychotic drugs: relation to clinical potencies. Psychopharmacology 95: 459–462.PubMedCrossRefGoogle Scholar
  12. Christensen AV, Arnt J, Hyttel J, Larsen JJ, Svendsen O (1984) Pharmacological effects of a specific dopamine D1 antagonist SCH 23390 in comparison with neuroleptics. Life Sci 39: 1529–1540.CrossRefGoogle Scholar
  13. Clark D, Hjorth S, Carlsson A (1985a) Dopamine receptor agonists: mechanisms underlying autoreceptor selectivity. I. Review of the evidence. J Neural Transm 62: 1–52.PubMedCrossRefGoogle Scholar
  14. Clark D, Hjorth S, Carlsson A (1985b) Dopamine receptor agonists: mechanisms underlying autoreceptor selectivity. II. Theoretical considerations. J NeuralTransm 62: 171–207.CrossRefGoogle Scholar
  15. Colpaert FC, Niemegeers CJE, Janssen PAJ (1982) A drug discrimination analysis of lysergic acid diethylamide (LSD): in vivo agonist and antagonist effects of purported 5-hydroxytryptamine antagonists and of pirenperone, an LSD antagonist. J Pharmacol Exp Ther 221: 206–214.PubMedGoogle Scholar
  16. Colpaert FC, Meert TF, Niemegeers CJE, Janssen PAJ (1985) Behavioral and 5-HT antagonist effects of ritanserin: a pure and selective antagonist of LSD discrimination in rats. Psychopharmacology 86: 45–54.PubMedCrossRefGoogle Scholar
  17. Coppen A, Prange AJ, Whybrow PC, Noguera R, Paez JM (1969) Methysergide in mania. A controlled trial. Lancet II: 338–340.CrossRefGoogle Scholar
  18. Costall B, Fortune DH, Naylor RJ, Marsden CD, Pycock C (1975) Serotonergic involvement with neuroleptic catalepsy. Neuropharmacology 14: 859–868.PubMedCrossRefGoogle Scholar
  19. Critchley MAE, Handley SE (1987) Effects in the X-maze anxiety model of agents acting at 5-HT1, and 5-HT2 receptors. Psychopharmacology 93: 502–506.PubMedCrossRefGoogle Scholar
  20. Deberdt R (1976) Pipamperone (Dipiperon) in the treatment of behaviour disorders. A large-scale multicentre evaluation. Acta Psychiat Belg 76: 157–166.Google Scholar
  21. Declerck AC, Wauquier A, Van der Haes-Veltman PHM, Gelders Y (1987) Increase in slow-wave sleep in humans with the serotonin S2 antagonist ritanserin. Curr Ther Res 41: 427–432.Google Scholar
  22. De Cuyper HJA (1989) Risperidone in the treatment of chronic psychotic patients: an overview of the double-blind comparative studies. In: Ayd FJ (ed) 30 years Janssen Research in Psychiatry. Ayd Medical Communications, Baltimore, pp 115–122.Google Scholar
  23. Dewhurst WG (1968) Methysergide in mania. Nature 219: 506–507.PubMedCrossRefGoogle Scholar
  24. Dugovic C, Wauquier A (1987) 5-HT2 receptors could be primarily involved in the regulation of slow wave sleep in the rat. Eur J Pharmacol 137: 145–146.PubMedCrossRefGoogle Scholar
  25. Ehringer RH, Hornykiewicz O (1960) Verteilung von Noradrenalin und Dopamin (3-Hydroxytyramin) im Gehirn des Menschen und ihr Verhalten bei Erkrankungen des extrapyramidalen Systems. Klin Wochenschr 15: 1236–1239.CrossRefGoogle Scholar
  26. Farde L, Wiesel FA, Halldin C, Sedvall G (1988) Central D2 dopamine receptor occupancy in schizophrenic patients treated with antipsychotic drugs. Arch Gen Psychiatry 45: 71–76.PubMedCrossRefGoogle Scholar
  27. Farde L, Wiesel FA, Nordström AL, Sedvall G (1989) D1- and D2-dopamine receptor occupancy during treatment with conventional and atypical neuroleptics. Psychopharmacology 99: S28–S31.PubMedCrossRefGoogle Scholar
  28. Fischer-Cornelssen KA, Ferner U (1976) An example of European multicenter trials (multi-spectral analysis of clozapine). Psychopharmacol Bull 12: 34–39.PubMedGoogle Scholar
  29. Fish B, Campbell M, Shapiro T, Floyd A (1969) Schizophrenic children treated with methysergide (Sansert). Dis Nerv Syst 30: 534–540.PubMedGoogle Scholar
  30. Gallant DM, Bishop MP (1968) Cinanserin (Sch 10.643): a preliminary evaluation in chronic schizophrenic patients. Curr Ther Res 10: 461–463.PubMedGoogle Scholar
  31. Gallant DM, Bishop MP, Steele CA, Noblin CD (1963) The relationship between serotonin antagonism and tranquillizing activity. Am J Psychiatry 119: 882.PubMedGoogle Scholar
  32. Gelders YE, Heylen SLE, Van den Bussche G, Reyntjens AJM, Janssen PAJ (1989) Risperidone, a breakthrough in antipsychotic therapy. In: Ayd FJ (ed) 30 years Janssen Research in Psychiatry. Ayd Medical Communications, Baltimore, pp 123–128.Google Scholar
  33. Gelders Y, Van den Bussche G, Reyntjens A, Janssen P (1986) Serotonin-S2 receptor blokkers in the treatment of chronic schizophrenia. Clin Neuropharmacol 9 (Suppl 4): 325–327.Google Scholar
  34. Haskovec L, Soucek K (1968) Trial of methysergide in mania. Nature 219: 507–508.PubMedCrossRefGoogle Scholar
  35. Hjorth SA, Carlsson A, Clark D et al. (1983) Central dopamine receptor agonist and antagonist action of the enantiomers of 3PPP. Psychopharmacology 81: 89–99.PubMedCrossRefGoogle Scholar
  36. Hjorth SA, Carlsson A, Wikström H et al. (1981) 3PPP, a new centrally acting DA-receptor agonist with selectivity for autoreceptors. Life Sci 28: 1225–1238.PubMedCrossRefGoogle Scholar
  37. Holden JMC, Itil T, Keskiner A, Gannon P (1971) A critical trial of an antiserotonin compound, cinanserin, in chronic schizophrenia. J Clin Pharmacol 11: 220–226.Google Scholar
  38. Hyttel J (1983) SCH 23390, the first selective dopamine D1 antagonist. Eur J Pharmacol 91: 153–154.PubMedCrossRefGoogle Scholar
  39. Idzikowski C, Cowen PJ, Nutt D, Mills FJ (1987) The effect of chronic ritanserin treatment on sleep and the neuroendocrine response to L-tryptophan. Psychopharmacology 93: 416–420.PubMedCrossRefGoogle Scholar
  40. Idzikowski C, Mills FJ, Glennard R (1986) 5-Hydroxytryptamine-2-antagonist increases human slow wave sleep. Brain Res 378: 164–168.PubMedCrossRefGoogle Scholar
  41. Iorio LC, Barnett A, Leitz FH, Houser VT, Korduba CA (1983) SCH 23390, a potential benzazepine antipsychotic with unique interaction on dopaminergic systems. J Pharmacol Exp Ther 226: 462–468.PubMedGoogle Scholar
  42. Iversen LL (1975) Dopamine receptors in the brain. A dopamine-sensitive adenylate cyclase models synaptic receptors, illuminating antipsychotic drug action. Science 188: 1084–1089.PubMedCrossRefGoogle Scholar
  43. Janssen PAJ (1987a) Does ritanserin, a potent serotonin S2 antagonist, restore energetic functions during the night. JR Soc Med 80: 409–413.Google Scholar
  44. Janssen PAJ (1987b) The development of new antipsychotic drugs: towards a new strategy in the management of chronic psychoses. J Drug Ther Res 12: 324–328.Google Scholar
  45. Janssen PAJ (1988) Die Entwicklung neuartiger Antipsychotika — ein Schritt vorwärts in der Behandlung chronischer Psychosen. In: Bergener M (ed) Fortschritt in der Behandlung chronischer Psychosen. Perimed, Erlangen, S 34–42.Google Scholar
  46. Janssen PAJ, Niemegeers CJE, Awouters F, Schellekens KHL, Megens AAHP, Meert TF (1988) Pharmacology of risperidone (R 64766), a new antipsychotic with serotonin-S2 and dopamine-D2 antagonistic properties. J Pharmacol Exp Ther 244: 685–693.PubMedGoogle Scholar
  47. Kane J, Honigfeld G, Singer J, Meltzer H, The Clozaril Collaborative Study Group (1988) Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch GenPsychiatry 45: 789–796.CrossRefGoogle Scholar
  48. Kebabian JW, Calne DB (1979) Multiple receptors for dopamine. Nature 277: 93–96.PubMedCrossRefGoogle Scholar
  49. Köhler C, Haglund L, Ögren SDO, Ängeby T (1981) Regional blockade by neuroleptic drugs of “in vivo” 3H-spiperone binding in the rat brain. Relation to blockade of apomorphine induced hyperactivity. J Neural Transm 52: 163–173.PubMedCrossRefGoogle Scholar
  50. Le Fur G, Guilloux F, Uzan A (1980) In vivo blockade of dopaminergic receptors from different rat brain regions by classical and atypical neuroleptics. Biochem Pharmacol 29: 267–270.PubMedCrossRefGoogle Scholar
  51. Leysen JE, Laduron PM (1977) A serotonergic component of neuroleptic receptors. Arch Int Pharmacol Ther 230: 337–339.Google Scholar
  52. Leysen JE, Niemegeers CJE (1985) Neuroleptics. In: Lajtha A (ed) Handbook of neurochemistry, vol 9, chapt 13. Plenum, New York, pp 331–361.Google Scholar
  53. Leysen JE, Gommeren W, Van Gompel P, Wynants J, Janssen PFM, Laduron PM (1985) Receptor binding properties in vitro and in vivo of ritanserin. A very potent and long acting serotonin-S2 antagonist. Mol Pharmacol 27: 600–611.PubMedGoogle Scholar
  54. Leysen JE, Gommeren W, Eens A, de Chaffoy de Courcelles D, Stoof JC, Janssen PAJ (1988) Biochemical profile of risperidone, a new antipsychotic. J Pharmacol Exp Ther 247: 661–670.PubMedGoogle Scholar
  55. Leysen JE, Niemegeers CJE, Tollenaere JP, Laduron PM (1978) Serotonergic component of neuroleptic receptors. Nature 272: 168–171.PubMedCrossRefGoogle Scholar
  56. Maire FW, Collins LG, Marks JB (1967) Evaluation of the drug 1-methyl-d-lysergic acid butanolamide or methysergide maleate in the treatment of chronic schizophrenia. Int J Neurophysiol 3: 397–399.Google Scholar
  57. Maj J, Mogilnicka E, Przewlocka B (1975) Antagonistic effect of cyproheptadine in neuroleptic induced catalepsy. Pharmacol Biochem Behav 3: 25–37.PubMedCrossRefGoogle Scholar
  58. Meco G, Bedini L, Bonifati V, Sonsini U (1989) Risperidone in the treatment of chronic schizophrenia with tardive dyskinesia. Curr Ther Res 46: 876–883.Google Scholar
  59. Meert TF (1986) A comparative study of the effects of ritanserin (R 55667) and chlordiazepoxide on rat open field behavior. Drug Dev Res 8: 197–204.CrossRefGoogle Scholar
  60. Meert TF, Colpaert FC (1986) The shock probe conflict procedure. A new assay responsive to benzodiazepines, barbiturates and related compounds. Psychopharmacology 88: 445–450.PubMedCrossRefGoogle Scholar
  61. Mendels J (1967) The effect of methysergide (an antiserotonin agent) on schizophrenia: a preliminary report. Am J Psychiatry 124: 849–852.PubMedGoogle Scholar
  62. Mesotten F, Suy E, Pietquin M, Burton P, Heylen S, Gelders Y (1989) Therapeutic effect and safety of increasing doses of risperidone (R 64766) in psychiatric patients. Psychopharmacology 99: 445–449.PubMedCrossRefGoogle Scholar
  63. Niemegeers CJE, Janssen PAJ (1979) A systematic study of the pharmacological activities of dopamine antagonists. Life Sci 24: 2201–2216.PubMedCrossRefGoogle Scholar
  64. Pangalila-Ratu Langi EA, Jansen AAI (1988) Ritanserin in the treatment of generalized anxiety disorders: a placebo-controlled trial. Hum Psychopharmacol 3: 207–212.CrossRefGoogle Scholar
  65. Peroutka SJ, Snyder SH (1979) Multiple serotonin receptors: differential binding of [3H]5-hydroxytryptamine, [3H]lysergic acid diethylamide and [3H]spiroperidol. Mol Pharmacol 16: 687–699.PubMedGoogle Scholar
  66. Persyko I (1972) Psychiatric adverse reaction to methysergide. J Nerv Ment Dis 154: 299–301.PubMedCrossRefGoogle Scholar
  67. Rapport MM (1949) Serum vasoconstrictor (serotonin) V. The presence of creatinine in the complex. A proposed structure of the vasoconstriction principle. J Biol Chem 180: 961–969.Google Scholar
  68. Reyntjens A, Gelders YG, Hoppenbrouwers M-LJA, Van den Bussche G (1986) Thymosthenic effects of ritanserin (R 55667), a centrally acting serotonin S2 receptor blocker. Drug Dev Res 8: 205–211.CrossRefGoogle Scholar
  69. Roose K, Gelders Y, Heylen S (1988) Risperidone (R 64766) in psychotic patients: a first clinical therapeutic exploration. Acta Psychiat Belg 88: 233–241.Google Scholar
  70. Seeman P (1980) Brain dopamine receptors. Pharmacol Rev 32: 229–313.PubMedGoogle Scholar
  71. Squelart P, Saravia J (1977) Pipamperone (Dipiperon), a useful sedative neuroleptic drug in troublesome and chronic psychotic patients. Acta Psychiat Belg 77: 284–293.Google Scholar
  72. Tedeschi DH, Tedeschi RE, Fellows EJ (1961) Central serotonin antagonist activity of a number of phenothiazines. Arch Int Pharmacodyn 132: 172–179.PubMedGoogle Scholar
  73. Waddington JL (1988) Therapeutic potential of selective D1 dopamine receptor agonists and antagonists in psychiatry and neurology. Gen Pharmacol 19: 55–60.PubMedCrossRefGoogle Scholar
  74. Waldmeier PC, Delini-Stula AA (1979) Serotonin-dopamine interactions in the nigrostriatal system. Eur J Pharmacol 55: 363–373.PubMedCrossRefGoogle Scholar
  75. Woolley DW (1962) The biochemical bases of psychoses. On the serotonin hypothesis about mental diseases. Wiley, New York, pp 131–192.Google Scholar
  76. Woolley DW, Shaw E (1954) A biochemical and pharmacological suggestion about certain mental disorders. Proc Nat Acad Sci 40: 228–231.PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • C. J. E. Niemegeers
  • F. Awouters
  • P. A. J. Janssen

There are no affiliations available

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