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Psychopharmacology

, Volume 106, Issue 4, pp 433–438 | Cite as

Time course of D2-dopamine receptor occupancy examined by PET after single oral doses of haloperidol

  • Anna-Lena Nordström
  • Lars Farde
  • Christer Halldin
Original Investigations

Abstract

Central D2-dopamine receptor occupancy was followed by repeated PET experiments after administration of single oral doses of haloperidol to four healthy men. D2-dopamine receptor occupancy was high already 3 h after administration of 4 and 7.5 mg haloperidol and remained high for at least 27 h. Akathisia appeared when D2-dopamine receptor occupancy was maximal. After initiation of neuroleptic drug treatment several days or weeks may elapse before antipsychotic effect is evident. The results of this study do not indicate that any late onset of the antipsychotic effect is related to an insufficient D2-dopamine receptor occupancy during the first days of treatment.

Key words

D2-dopamine receptors Human subjects Positron emission tomography Haloperidol Brain 

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References

  1. Barnes TRE (1989) A rating scale for drug-induced akathisia. Br J Psychiatry 154:672–676PubMedGoogle Scholar
  2. Bergström M, Boëthius J, Eriksson L, Greitz T, Ribbe T, Widén L (1981) Head fixation device for reproducible position alignment in transmission CT and positron emission tomography. J Comput Assist Tomogr 5:136–141PubMedGoogle Scholar
  3. Bohm C, Greitz T, Blomquist G, Farde L, Forsgren PO, Kingsley D, Sjögren I, Wiesel F-A, Wik G (1986) Applications of a computerized adjustable brain atlas in positron emission tomography. Acta Radiol Suppl 369:449–452PubMedGoogle Scholar
  4. Braude WM, Barnes TRE, Gore SM (1983) Clinical characteristics of akathisia. Br J Psychiatry 143:139–150PubMedGoogle Scholar
  5. Bunney BS (1984) Antipsychotic drug effects on the electrical activity of dopamine neurons. TINS 7:212–215Google Scholar
  6. Carlsson A, Lindquist M (1963) Effect of chlorpromazine or haloperidol on formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta Pharmacol Toxicol 20:140–144Google Scholar
  7. Creese I, Burt DR, Snyder SH (1976) Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 192:481–483Google Scholar
  8. Farde L, von Bahr C (1990) Distribution of remoxipride to the human brain and central D2-dopamine receptor binding examined in vivo by PET. Psychiatr Scand 82:67–71Google Scholar
  9. Farde L, Ehrin E, Eriksson L, Greitz T, Hall H, Hedström C-G, Litton J-E, Sedvall G (1985) Substituted benzamides as ligands for visualization of dopamine receptor binding in the human brain by positron emission tomography. Proc Natl Acad Sci USA 82:3863–3867PubMedGoogle Scholar
  10. Farde L, Pauli S, Hall H, Stone-Elander S, Eriksson L, Halldin C, Högberg T, Nilsson L, Sjögren I (1988a) Stereoselective binding for11C-raclopride in living human brain — a search for extrastriatal central D2-dopamine receptors by PET. Psychopharmacology 94:471–478CrossRefPubMedGoogle Scholar
  11. Farde L, Wiesel F-A, Halldin C, Sedvall G (1988b) Central D2-dopamine receptor occupancy in schizophrenic patients treated with antipsychotic drugs. Arch Gen Psychiatry 45:71–76PubMedGoogle Scholar
  12. Farde L, Wiesel F-A, Nordström A-L, Sedvall G (1989) D1- and D2-dopamine receptor occupancy during treatment with conventional and atypcial neuroleptics. Psychopharmacology 99:S28-S31CrossRefPubMedGoogle Scholar
  13. Farde L, Wiesel F-A, Stone-Elander S, Halldin C, Nordström A-L, Hall H, Sedvall G (1990) D2-dopamine receptors in neurolepticnaive schizophrenic patients. Arch Gen Psychiatry 47:213–219PubMedGoogle Scholar
  14. Johnstone EC, Crow TJ, Ferrier IN, Frith CD, Owens DGC, Bourne RC, Gamble SJ (1983) Adverse effects of anticholinergic medication on positive schizophrenic symptoms. Psychol Med 13:513–527PubMedGoogle Scholar
  15. Kendler KS (1976) A medical student's experience with akathisia. Am J Psychiatry 133:454–455Google Scholar
  16. Larsson M, Forssman A, Öhman R (1983) A high-performance liquid chromatographic method for the determination of haloperidol and reduced haloperidol in serum. Curr Ther Res 34:999–1008Google Scholar
  17. Litton J, Bergström M, Eriksson L, Bohm C, Blomqvist G, Kesselberg M (1984) Performance study of the PC-384 positron camera system for emission tomography of the brain. J Comput Assist Tomogr 8:74–87PubMedGoogle Scholar
  18. Peroutka SJ, Snyder SH (1980) Relationship of neuroleptic drug effects at brain dopamine, serotonin, α-adrenergic, and histamine receptors to clinical potency. Am J Psychiatry 261:1518–1522Google Scholar
  19. Sassin JF, Frantz AG, Weitzman ED, Kapen S (1972) Human prolactin: 24-hour pattern with increased release during sleep. Science 177:1205–1207PubMedGoogle Scholar
  20. Seeman P, Lee T, Chau-Wong M, Wong K (1976) Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature 261:717–719CrossRefPubMedGoogle Scholar
  21. Tolis G (1980) Prolactin: physiology and pathology. Hosp Pract 15:85–95Google Scholar
  22. van Rossum JM (1966) The significance of dopamine receptor blockade for the mechanism of action of neuroleptic drugs. Arch Int Pharmacodyn Ther 160:492–494PubMedGoogle Scholar
  23. Wode-Helgoth B, Borg S, Fyrö B, Sedvall G (1978) Clinical effects and drug concentrations in plasma and cerebrospinal fluid in psychotic patients treated with fixed doses of chlorpromazine. Acta Psychiatr Scand 58:149–173PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Anna-Lena Nordström
    • 1
  • Lars Farde
    • 1
  • Christer Halldin
    • 1
  1. 1.Ulf Lundahl Research Unit, Department of Psychiatry and PsychologyThe Karolinska InstituteStockholmSweden

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