Sertindole and dopamine D2 receptor occupancy in comparison to risperidone, clozapine and haloperidol - a 123I-IBZM SPECT study.
The striatal D2 dopamine binding was studied in schizophrenic patients treated with the novel atypical antipsychotic drug sertindole (n=10). Comparisons were obtained with haloperidol (n=8), clozapine (n=6), risperidone (n=11) and untreated healthy controls (n=8) of a dataset which has partly been reported previously. 123I-Iodobenzamide (IBZM) single photon emission computerized tomography (SPECT) was used for estimation of striatal dopamine D2 receptor binding. Sertindole-treated patients exhibited significantly (P < 0.001) lower levels of striatal D2 binding (BG/FC ratio:1.28) compared with those treated with haloperidol (BG/FC ratio:1.09) and risperidone (8 mg:1.18) but significantly (P < 0.005) higher levels compared with clozapine (BG/FC ratio: 1.49). However, if patients were pretreated with a depot neuroleptic, significantly (P < 0.05) higher striatal D2 binding (BG/FC ratio:1.12) has been obtained. Since sertindole has been shown to exert distinct clinical efficacy for treatment of positive and negative symptoms, our data are indicative that antipsychotic efficacy is not associated with a high degree of striatal D2 receptor occupancy in schizophrenic patients.
Kasper
S
S
Department of General Psychiatry, University of Vienna, Austria.
Tauscher
J
J
Küfferle
B
B
Barnas
C
C
Hesselmann
B
B
Asenbaum
S
S
Podreka
I
I
Brücke
T
T
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001549:Benzamides; D003024:Clozapine / Q000378:metabolism; D005260:Female; D006220:Haloperidol / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000378:metabolism / Q000627:therapeutic use*; D007211:Indoles / Q000378:metabolism / Q000627:therapeutic use*; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D018967:Risperidone / Q000378:metabolism; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon
D014150:Antipsychotic Agents; D001549:Benzamides; D007093:Imidazoles; D007211:Indoles; D007457:Iodine Radioisotopes; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; C066304:sertindole; D003024:Clozapine; D006220:Haloperidol; D018967:Risperidone