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  • Title: Higher occupancy of muscarinic receptors by olanzapine than risperidone in patients with schizophrenia. A[123I]-IDEX SPECT study.
    Author: Lavalaye J, Booij J, Linszen DH, Reneman L, van Royen EA.
    Journal: Psychopharmacology (Berl); 2001 Jun; 156(1):53-7. PubMed ID: 11465633.
    Abstract:
    RATIONALE: In vitro data have shown anticholinergic properties of the atypical antipsychotic drug olanzapine. Substantial occupancy of muscarinic receptors may be an explanation for the low incidence of extrapyramidal side effects induced by olanzapine. OBJECTIVES: To obtain an in vivo measurement of muscarinic receptor occupancy by olanzapine compared with risperidone in patients with schizophrenia stabilised on medication. METHODS: Five patients with schizophrenia treated with olanzapine and five patients treated with risperidone were studied. Muscarinic receptor occupancy in the striatum and cortex was studied in vivo with SPECT using [123I]-IDEX as a radioligand. SPECT data were compared with those of six healthy subjects. RESULTS: Patients stabilised on olanzapine showed significantly lower mean (+/-SD) striatal and cortical (1.50+/-0.21 and 1.51+/-0.22, respectively) muscarinic receptor binding ratios of [123I]-IDEX (reflecting higher levels of muscarinic receptor occupancy) than controls (3.91+/-0.61 and 3.65+/-0.70, respectively). Furthermore, [123I]-IDEX binding ratios in patients treated with risperidone were slightly lower than controls, reaching significance only in the striatum (2.99+/-0.27 versus 3.91+/-0.61, for risperidone and controls). CONCLUSIONS: The substantial occupancy of muscarinic receptors in the striatum and cortex by olanzapine may be an explanation for the low incidence and severity of extrapyramidal side effects of this antipsychotic drug. Furthermore, it may also explain the anticholinergic side effects of olanzapine.
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