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Binding of 3H-neuroleptics and 3H-apomorphine in schizophrenic brains

Nature volume 274, pages 897900 (31 August 1978) | Download Citation

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Abstract

THE neuroleptic or antipsychotic drugs, introduced in 19521, effectively prevent relapse and rehospitalisation of schizophrenic patients. These drugs provide a strategy2 for localising possible abnormalities in the brain in schizophrenia. The hypothesis that schizophrenia might be associated with abnormally sensitive dopamine synapses3–6 evolved from the suggestion that neuroleptics block dopamine receptors and thus accelerate the turnover of dopamine7,8. The hypothesis received additional support from the observations that dopamine-mimetic drugs (for example d-amphetamine, L-dopa) elicit or exacerbate psychotic symptoms9–12, that neuroleptics produce supersensitivity to dopamine13–15, that the neuroleptic and antipsychotic actions are enhanced by drugs which block the synthesis of catecholamines16, that neuroleptics all have conformations that match that of dopamine17, and that dopamine is the most potent neurotransmitter to inhibit the specific binding of 3H-haloperidol to dopamine-rich regions of the brain18–20. Although all this evidence for the dopamine hypothesis of schizophrenia is circumstantial, we have now obtained direct evidence for some abnormalities in brain dopamine receptors in schizophrenia by measuring the specific binding of 3H-apomorphine and 3H-haloperidol or 3H-spiperone to four regions of postmortem brains from schizophrenic patients.

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References

  1. 1.

    , & Ann. Méd.-Psychol. 110, 267–273 (1952).

  2. 2.

    Int. Rev. Neurobiol. 9, 145–221 (1966).

  3. 3.

    & Orthomolec. Psychiat. 1, 2–7 (1972).

  4. 4.

    & A. Rev. Med. 551–565 (1975).

  5. 5.

    Adv. Biochem. Psychopharmac. 16, 667–669 (1977).

  6. 6.

    A. Rev. Pharmac. Toxic. 17, 545–559 (1977).

  7. 7.

    Archs Int. Pharmacodyn. 160, 492–494 (1966).

  8. 8.

    & Acta pharmac. toxic. 20, 140–144 (1963).

  9. 9.

    , & Curr. Ther. Res. 12, 528–531 (1970).

  10. 10.

    Am. J. Psychiat. 133, 197–202 (1976).

  11. 11.

    , , & Psychopharmacologia (Berl.) 44, 273–280 (1975).

  12. 12.

    & Archs gen. Psychiat. 33, 304–308 (1976).

  13. 13.

    & Neuropharmacology 13, 927–940 (1974).

  14. 14.

    , , & Psychopharmacologia (Berl.) 41, 97–104 (1975).

  15. 15.

    , , & Psychopharmacologia (Berl.) 45, 151–155 (1975).

  16. 16.

    , , & J. Neural Trans. 33, 83–90 (1972).

  17. 17.

    , & J. Pharm. Pharmac. 27, 553–563 (1975).

  18. 18.

    , , & Nature 261, 717–719 (1976).

  19. 19.

    Biochem. Pharmac. 26, 1741–1748 (1977).

  20. 20.

    , & Molec. Pharmac. 12, 800–812 (1976).

  21. 21.

    , , , & Proc. natn. Acad. Sci. U.S.A. 73, 4354–4358 (1976).

  22. 22.

    & Biochem. Pharmac. 26, 1003–1007 (1977).

  23. 23.

    et al. Lancet ii, 1157–1159 (1977).

  24. 24.

    & Soc. Neurosci. 6, 874 (1976).

  25. 25.

    , & Science 196, 326–328 (1976).

  26. 26.

    & Life Sci. 21, 1751–1758 (1977).

  27. 27.

    , , & Nature 274, 278–281 (1978).

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Author information

Affiliations

  1. Department of Pharmacology, University of Toronto, Toronto, Canada, M5S 1A8

    • TYRONE LEE
    •  & PHILIP SEEMAN
  2. Wadsworth Hospital, Los Angeles

    • W. W. TOURTELLOTTE
  3. Clarke Institute of Psychiatry, 250 College Street, Toronto, Ontario, Canada

    • IRENE J. FARLEY
    •  & OLEH HORNYKEIWICZ
  4. Present address: Institute of Biochemical Pharmacology, University of Vienna, Vienna, A-1090, Austria.

    • OLEH HORNYKEIWICZ

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https://doi.org/10.1038/274897a0

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