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Regional selectivity of novel antipsychotics

Published online by Cambridge University Press:  02 January 2018

M. Kopeček
Affiliation:
Psychiatric Centre Prague, Ústavní 91, 181 03 Praha 8-Bohnice, Czech Republic
C. Höschl
Affiliation:
Psychiatric Centre Prague, Ústavní 91, 181 03 Praha 8-Bohnice, Czech Republic
T. Hájek
Affiliation:
Psychiatric Centre Prague, Ústavní 91, 181 03 Praha 8-Bohnice, Czech Republic
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Abstract

Type
Columns
Copyright
Copyright © Royal College of Psychiatrists, 2002 

Xiberas et al (Reference Xiberas, Martinot and Mallet2001) measured D2 receptor occupancy in striatum, thalamus and temporal cortex in patients treated with haloperidol, risperidone, amisulpride, clozapine and olanzapine. On the basis of their findings, they conclude that in the striatum and in the thalamus atypical antipsychotics induce a significantly lower D2 binding index than haloperidol does. Their results are consistent with previous studies showing only small differences between striatal and temporal cortex blockade by traditional compounds and relatively selective D2 blockade in temporal cortex caused by atypical antipsychotics (Reference Pilowsky, Mulligan and ActonPilowsky et al, 1997; Reference Bigliani, Mulligan and ActonBigliani et al, 2000).

Looking at the data from Xiberas et al (Reference Xiberas, Martinot and Mallet2001), we came to different conclusions. Using equipotent doses of antipsychotics (doses which lead to the same occupation of D2 receptors in the striatum), no differences in thalamo-striatal and temporostriatal indices between typical and atypical antipsychotics could be shown (Table 1). We suggest that atypical antipsychotics do not exert special temporal lobe or limbic selectivity. The selectivity depends more on the dose than on the type of antipsychotic (typical v. atypical). This is in agreement with Nyberg & Farde (Reference Nyberg and Farde2000) and Geddes et al (Reference Geddes, Freemantle and Harrison2000), who argue that non-equipotent doses can partly explain differences between classical and novel antipsychotics.

Table 1 D2 dopamine receptor binding indices in striatum, thalamus and temporal cortex, and the ratios of temporal/striatal (temporo-striatal) and thalamic/striatal (thalamo-striatal) binding indices in patients taking traditional and atypical antipsychotics (data from Reference Xiberas, Martinot and MalletXiberas et al, 2001)

Drug Binding index (%)
Striatum Thalamus Temporal cortex Temporo-striatal index Thalamo-striatal index
Haloperidol 3 mg 66.6 91.2 88.3 1.33 1.37
Risperidone 6 mg 67 92.2 92.2 1.38 1.38
Amisulpride 1000 mg 61.5 69.9 87.8 1.43 1.14
Olanzapine 20 mg 69.6 91.9 91.8 1.32 1.32
Clozapine 200 mg 45.9 79 90.1 1.96 1.72

References

Bigliani, V., Mulligan, R. S., Acton, P. D., et al(2000) Striatal and temporal cortical D2/D3 receptor occupancy by olanzapine and sertindole in vivo: a [1231] epidepride single photon emission tomography (SPET) study. Psychopharmacology, 150, 132140.CrossRefGoogle ScholarPubMed
Geddes, J., Freemantle, N., Harrison, P., et al (2000) Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis. BMJ, 321, 13711376.CrossRefGoogle ScholarPubMed
Nyberg, S. & Farde, L. (2000) Non-equipotent doses partly explain differences among antipsychotics – implications of PET studies. Psychopharmacology, 148, 2223.Google ScholarPubMed
Pilowsky, L. S., Mulligan, R. S., Acton, P. D., et al (1997) Limbic selectivity of clozapine. Lancet, 350, 490491.CrossRefGoogle ScholarPubMed
Xiberas, X., Martinot, J. L., Mallet, L., et al (2001) Extrastriatal and striatal D2 dopamine receptor blockade with haloperidol or new antipsychotic drugs in patients with schizophrenia. British Journal of Psychiatry, 179, 503508.CrossRefGoogle ScholarPubMed
Figure 0

Table 1 D2 dopamine receptor binding indices in striatum, thalamus and temporal cortex, and the ratios of temporal/striatal (temporo-striatal) and thalamic/striatal (thalamo-striatal) binding indices in patients taking traditional and atypical antipsychotics (data from Xiberas et al, 2001)

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