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Striatal and extra-striatal D2/D3 dopamine receptor occupancy by quetiapine in vivo: [123I]-epidepride single photon emission tomography (SPET) study

  • C. M. E. Stephenson (a1), V. Bigliani (a1), H. M. Jones (a1), R. S. Mulligan (a2), P. D. Acton (a3), D. Visvikis (a2), P. J. Ell (a2), R. W. Kerwin (a1) and L. S. Pilowsky (a1)...

Extract

Background

Selective action at limbic cortical dopamine D2-like receptors could mediate atypical antipsychotic efficacy with few extrapyramidal side-effects.

Aims

To test the hypothesis that quetiapine has ‘limbic selective’ D2/D3 receptor occupancy in vivo.

Method

The high-affinity D2/D3 ligand [123I]-epidepride and single photon emission tomography were used to estimate D2/D3 specific binding and an index of relative percentage D2/D3 occupancy in striatal and temporal cortical regions for quetiapine-treated patients (n=6). Quetiapine-, and previously studied typical-antipsychotic- and clozapine-treated patients were compared.

Results

Mean (s.d.) relative percentage D2/D3 receptor occupancy by quetiapine was 32.0% (14.6) in striatum and 60.1% (17.2) in temporal cortex (mean daily dose 450 mg: range 300–700 mg/day). Quetiapine treatment resulted in limbic selective D2/D3 blockade similar to clozapine and significantly higher than typical antipsychotics.

Conclusions

Preliminary data suggest that limbic selective D2/D3 receptor blockade is important for atypical drug action.

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Copyright

Corresponding author

C. M. E. Stephenson, c/o L. S. Pilowsky, Department of Psychological Medicine, Section of Neurochemical Imaging, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK

Footnotes

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Declaration of interest

C.M.E.S. and H.M.J. were supported by research grants from AstraZeneca, V.B. by a research grant from Eli Lilly and R.S.M. by a UK Medical Research Council (MRC) Senior Clinical Research Fellowship Award. L.S.P. is a UK MRC Senior Clinical Research Fellow.

Footnotes

References

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Abi-Dargham, A., Kegeles, L., Zea-Ponce, Y., et al (1999) Imaging resting phasic dopamine synaptic activity in schizophrenia. Schizophrenia Research, 36, 239.
Alcohol, Drug Abuse, and Mental Health Administration (1974) Abnormal Involuntary Movements Scale (AIMS). Washington, DC: Department of Health, Education and Welfare.
American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders (4th edn) (DSM–IV). Washington, DC: APA.
Andreason, N. C. (1981) Scale for the Assessment of Negative Symptoms (SANS). Iowa City, IA: University of Iowa.
Andreason, N. C. (1984) Scale for the Assessment of Positive Symptoms (SAPS). Iowa City, IA: University of Iowa.
Aravintis, L. A., Miller, B. G. & Seroquel Trial 13 Study Group (1997) Multiple fixed doses of ‘Seroquel’ (Quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo. Biological Psychiatry, 42, 233246.
Barnes, T. R. E. (1989) A rating scale for drug-induced akathisia. British Journal of Psychiatry, 154, 672676.
Bigliani, V., Mulligan, R. S., Acton, P. D., et al (1999) In vivo occupancy of striatal and temporal cortical D2/D3 dopamine receptors by typical antipsychotic drugs: [123I]-epidepride single photon emission tomography (SPET) study. British Journal of Psychiatry, 175, 231238.
Camps, M., Cortes, R., Gueye, B., et al (1989) Dopamine receptors in human brain. Autoradiographic distribution of D2 sites. Neuroscience, 28, 275290.
Damasio, H. & Damasio, A. R. (1989) Lesion Analysis in Neuropsychology. New York: Oxford University Press.
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, 766771.
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, 396404.
Fujita, M., Seibyl, J. P., Verhoeff, N. P. L. G., et al (1999) Kinetic and equilibrium analyses of [123I]-epidepride binding to striatal and extrastriatal dopamine D2 receptors. Synapse, 34, 290304.
Gefvert, O., Bergstrom, M., Langstrom, B., et al (1998) Time course of central nervous dopamine-D2 and 5-HT2 receptor blockade and plasma drug concentrations after discontinuation of quetiapine (Seroquel) in patients with schizophrenia. Psychopharmacology, 135, 119126.
Goldsmith, S. K., Shapiro, R. M. & Joyce, J. N. (1997) Disrupted pattern of D2 dopamine receptors in the temporal lobe in schizophrenia: a postmortem study. Archives of General Psychiatry, 54, 649658.
Goldstein, J. (1995) Preclinical pharmacology of new atypical antipsychotics in late stage development. Experimental Opinion in Investigational Drugs, 4, 291298.
Hagberg, G., Gefvert, O., Bergstrom, M., et al (1998) N-[11C]Methylspiperone PET, in contrast to [11C]raclopride, fails to detect D2 receptor occupancy by an atypical neuroleptic. Psychiatry Research, 82, 147160.
Ichise, M., Fujita, M., Seibyl, J. P., et al (1999) Graphical analysis and simplified quantification of striatal and extrastriatal dopamine D2 receptor binding with [123I]epidepride SPECT. Journal of Nuclear Medicine, 40, 19021912.
Kornhuber, J., Brucke, T., Angelberger, P., et al (1995) SPECT imaging of dopamine receptors with [123I]-epidepride: characteristics of uptake in the human brain. Journal of Neural Transmission, 101, 95103.
Kufferle, B., Tauscher, J., Asenbaum, S., et al (1997) IBZM SPECT imaging of striatal dopamine-2 receptors in psychotic patients treated with the novel antipsychotic substance quetiapine in comparison to clozapine and haloperidol. Psychopharmacology, 133, 323328.
Laruelle, M., Abi-Dargham, A., Gil, R., et al (1999) Increased dopamine transmission in schizophrenia: relationship to illness phase. Biological Psychiatry, 46, 5672.
Lidow, M. S., Williams, G. V. & Goldman-Rakic, P. S. (1998) The cerebral cortex: a case for a common site of action of antipsychotics. Trends in Pharmacological Sciences, 19, 136140.
Moghaddam, B., Berridge, C. W., Goldman-Rakic, P. S., et al (1993) in vivo assessment of basal and drug-induced dopamine release in cortical and subcortical regions of the anesthetized primate. Synapse, 13, 215222.
Montgomery, S. A. & Åsberg, M. (1979) A new depression scale designed to be sensitive to change. British Journal of Psychiatry, 134, 382389.
Overall, J. & Gorham, D. E. (1962) The brief psychiatric rating scale. Psychological Reports, 10, 799812.
Pilowsky, L. S., Mulligan, R. S., Acton, P. D., et al (1997) Limbic selectivity of clozapine. Lancet, 350, 490491.
Pilowsky, L. S., Bigliani, V., Mulligan, R. S., et al (1998) Clozapine preferentially occupies limbic cortical D2/D3 receptors in vivo: a 123I-epidepride SPET (single photon emission tomography). Journal of Psychopharmacology, 12 (suppl. A), A53.
Pirker, W., Asenbaum, S., Wenger, S., et al (1997) Iodine-123-epidepride-SPECT: studies in Parkinson's disease, multiple system atrophy and Huntington's disease. Journal of Nuclear Medicine, 38, 17111717.
Scatton, B., Claustre, Y., Cudennec, A., et al (1997) Amisulpride: from animal pharmacology to therapeutic action. International Journal of Clinical Psychopharmacology, 12 (suppl. 2), S29S36.
Schafer, R. A. & Levant, B. (1998) The D3 dopamine receptor in cellular and organismal function. Psychopharmacology, 135, 116.
Seeman, P. & Tallerico, T. (1999) Rapid release of antipsychotic drugs from dopamine D2 receptors: an explanation for low receptor occupancy and early clinical relapse upon withdrawal of clozapine or quetiapine. American Journal of Psychiatry, 156, 876884.
Simpson, G. H. & Angus, J. W. S. (1970) A rating scale for extra-pyramidal side effects. Acta Psychiatrica Scandinavica, 212 (suppl.), 1119.
Suhara, T., Sudo, Y., Okauchi, T., et al (1999) Extrastriatal dopamine D2 receptor density and affinity in the human brain measured by 3D PET. International Journal of Neuropsychopharmacology, 2, 7382.
Xiberas, X., Martinet, J. L., Pailliere-Martinot, M. L., et al (1999) In vivo interactions of antipsychotic drugs with the extrastriatal D2 dopamine receptors. Schizophrenia Research, 36, 249.

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Striatal and extra-striatal D2/D3 dopamine receptor occupancy by quetiapine in vivo: [123I]-epidepride single photon emission tomography (SPET) study

  • C. M. E. Stephenson (a1), V. Bigliani (a1), H. M. Jones (a1), R. S. Mulligan (a2), P. D. Acton (a3), D. Visvikis (a2), P. J. Ell (a2), R. W. Kerwin (a1) and L. S. Pilowsky (a1)...
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