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In vivo occupancy of striatal and temporal cortical D2/D3 dopamine receptors by typical antipsychotic drugs

[123I]-epidepride single photon emission tomography (SPET) study

Published online by Cambridge University Press:  03 January 2018

Valeria Bigliani ,
Rachel S. Mulligan ,
Paul D. Acton ,
Dimitris Visvikis ,
Peter J. Ell ,
Caroline Stephenson ,
Robert W. Kerwin  and
Lyn S. Pilowsky
Valeria Bigliani*
Affiliation:
Institute of Psychiatry, London
Rachel S. Mulligan
Affiliation:
Institute of Nuclear Medicine, University College London Medical School, London
Paul D. Acton
Affiliation:
Institute of Nuclear Medicine, University College London Medical School, London
Dimitris Visvikis
Affiliation:
Institute of Nuclear Medicine, University College London Medical School, London
Peter J. Ell
Affiliation:
Institute of Nuclear Medicine, University College London Medical School, London
Caroline Stephenson
Affiliation:
Institute of Psychiatry, London
Robert W. Kerwin
Affiliation:
Institute of Psychiatry, London
Lyn S. Pilowsky
Affiliation:
Institute of Psychiatry, London
*
Dr L. Pilowsky, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF. Fax: 0171-701 9044; e-mail: L.Pilowsky@iop.kcl.ac.uk
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Abstract

Background

The dopamine hypothesis proposes that antipsychotic drugs act primarily through limbic cortical D2/D2-like dopamine receptor blockade.

Aim

To evaluate this hypothesis with the D2/D3-selective SPET probe [123I]-epidepride.

Method

[123I]-epidepride SPETscans were performed on 12 patients with schizophrenia treated with antipsychotics and 11 age-matched healthy controls. [123I]-epidepride specific binding to D2/D3 dopamine receptors was estimated, and relative percentage D2/D3 receptor occupancy by typical antipsychotic drugs determined.

Results

Mean (s.d.) daily dose was 669.12 (516.8) mg chlorpromazine equivalents. Mean percentage D2/D3 receptor occupancy was 81.6 (8.1) and 73.2 (13.9) in the temporal cortex and striatum respectively.

Conclusions

Typical antipsychotic drug treatment is associated with substantial temporal cortical D2/D3 receptor occupancy. The relationship between this and efficacy is poor in patients with treatment-resistant schizophrenia.

Type
Papers
Information
The British Journal of Psychiatry , Volume 175 , Issue 3 , September 1999 , pp. 231 - 238
Copyright
Copyright © 1999 The Royal College of Psychiatrists 

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References

Alcohol, Drug Abuse, and Mental Health Administration (1974) Abnormal Involuntary Movements Scale (AIMS). Washington, DC: Department of Health, Education and Welfare.Google Scholar
American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders (4th edn) (DSM–IV). Washington. DC: APA.Google Scholar
Andreasen, N. C. (1983) Scale for the Assessment of Negative Symptoms (SANS). Iowa City. IA: University of Iowa.Google Scholar
Andreasen, N. C. (1984) Scale for the Assessment of Positive Symptoms (SAPS). Iowa City, IA: University of Iowa.Google Scholar
Barnes, T. R. E. (1989) A rating scale for drug-induced akathisia. British Journal of Psychiatry 154, 672–676.CrossRefGoogle ScholarPubMed
Bruche, T., Roth, J., Podrecka, I., et al (1992) Striatal dopamine D2 blockade by typical and atypical neuroleptics. Lancet, 339, 497.Google Scholar
Camps, M., Cortes, R., Gueye, B., et al (1989) Dopamine receptors in human brain. Autoradiographic distribution of D2 sites. Neuroscience, 28, 275–290.Google Scholar
Endicott, J., Spitzer, R. L., Fleiss, J. L., et al (1976) The Global Assessment Scale: a procedure for measuring overall severity of psychiatric disturbances. Archives of General Psychiatry, 33, 766–771.Google Scholar
Farde, L., Wiesel, F. A., Stone-Elander, S., et el (1998) D2 Dopamine receptors in neuroleptic-naive schizophrenic patients. Archives of General Psychiatry 47, 213–219.CrossRefGoogle Scholar
Farde, L., Nordstrom, A. L., Wiesel, A., et al (1992) Positron emission tomographic analysis of central D1 and D2-dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine: relation to extrapyramidal side effects. Archives of General Psychiatry 49, 538–543.Google Scholar
Farde, L., Suhara, T., Nyberg, S., et al (1997) A PET study of 11C-FLB-457 binding to extrastriatal D2 dopamine receptors in healthy subjects and antipsychotic drug-treated patients. Psychopharmacology 133, 396–404.Google Scholar
Hall, H., Farde, L., Halldin, C., et al (1996) Autoradiographic localisation of extrastriatal D2 dopamine receptors in the human brain using 125I-epidepride. Synapse, 23, 115–123.3.0.CO;2-C>CrossRefGoogle Scholar
Ito, H., Hietala, J., Blomqvist, G., et al (1998) Comparison of the transient equilibrium and continuous infusion method for quantitative PET analysis of [11C]-raclopride binding. Journal of Cerebral Blood Flow and Metabolism, 18, 941–949.Google Scholar
Kapur, S., Remington, G., Jones, C., et al (1996) High levels of dopamine D2 receptor occupancy with low dose haloperidol treatment: a PET study. American Journal of Psychiatry 153, 948–950.Google ScholarPubMed
Kapur, S., Zipursky, R., Roy, P., et al (1997) The relationship between D2 receptor occupancy and plasma levels on low dose oral haloperidol: a PET study. Psychopharmacology, 131, 148–152.CrossRefGoogle ScholarPubMed
Kessler, R. M., Whetsell, W. O., Sib Ansari, M., et al (1993) Identification of extrastriatal dopamine D2 receptors in post mortem human brain with 125I-epidepride. Brain Research, 609, 237–243.CrossRefGoogle Scholar
Kornhuber, J., Brucks, T., Angelberger, P., et al (1995) SPECT imaging of dopamine receptors with [123I]-epidepride: characterization of uptake in the human brain. Journal of Neural Transmission, 101. 95–103.CrossRefGoogle ScholarPubMed
Lidow, M. S. & Goldman-Rakic, P. S. (1994) A common action of clozapine, haloperidol and remaxipride on D-1 and D-2 dopaminergic receptors in the primate cerebral cortex. Proceedings of the National Academy of Sciences USA. 91, 4353–4356.Google Scholar
Martinot, J.-L., Palliere a Martinot, M. L., Loc'h, C., et al (1991) The estimated density of D2 striatal receptors in schizophrenia. A study with positron emission tomography and 76Br-bromolisuride. British Journal of Psychiatry, 158, 346–350.Google Scholar
Nordstrom, A. L., Farda, L., Wiesel, A., et al (1993) Central D2 dopamine receptor occupancy in relation to antipsychotic drug effect: a double blind PET study of schizophrenic patients. Biological Psychiatry, 33, 227–235.Google Scholar
Overall, J. & Gorham, D. E. (1962) The Brief Psychiatric Rating Scale. Psychological Reports, 10, 799–812.Google Scholar
Peroutka, S. J. & Synder, S. H. (1980) Relationship of neuroleptic drug effects at brain dopamine, serotonin, α-adrenergic, and histamine receptors to clinical potency. American Journal of Psychiatry, 137, 1518–1522.Google Scholar
Pilowsky, L. S., Costa, D., Eil, P., et al (1992) Clazapine, single photon emission tomography, and the D2 dopamine receptor blockade hypothesis of schizophrenia. Lancet, 340, 199–202.Google Scholar
Pilowsky, L. S., Costa, D., Eil, P., et al (1993) Antipsychotic medication, D2 dopamine receptor blockade and clinical response: a 123I-IBZM SPET (single photon emission tomography study). Psychological Medicine, 23, 791–797.Google Scholar
Pilowsky, L. S., Costa, D., Eil, P., et al (1994) D2 dopamine receptor binding in the basal ganglia of antipsychotic-free schizophrenic patients. An 123I-IBZM single photon emission computerised tomography study. British Journal of Psychiatry, 164, 16–26.Google Scholar
Pilowsky, L. S., Mulligan, R., Acton, P., et al (1997) Limbic selectivity of clozapine. Lancet. 350, 490–491.CrossRefGoogle ScholarPubMed
Pirkar, W., Asenbaum, S., Wanger, S., at al (1997) Iodine-123-epidepride-SPECT: studies in Parkinson's disease, multiple system atrophy and Huntington's disease. Journal of Nuclear Medicine, 38, 1711–1717.Google Scholar
Simpson, G. H. & Angus, J. W. S. (1970) A rating scale for extrapyramidal side-effects. Acta Psychiatrica Scandinavica, 212 (suppl.). 11–19.Google Scholar
Taylor, D., Karwin, R. & Duncan, D. (1996) The Maudsley Prescribing Guidelines (3rd edn). London: Bethlem and Maudsley NHS Trust.Google Scholar
Yousaf, K. A., Volkow, N. D., Schlyar, D. J., et al (1995) Haloperidol blocks the uptake of 16F-N-methylspiperdol by extrastriatal dopamine receptors in schizophrenic patients. Synapse, 19, 14–17.Google Scholar
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