title: Comparison of the in-vivo muscarinic cholinergic receptor availability in patients treated with clozapine and olanzapine.
abstract: Clozapine and olanzapine are two atypical antipsychotics that bind to a broad range of receptors in vitro. Our group previously reported on the binding of clozapine and olanzapine to muscarinic receptors in vivo. Based on these data, a direct comparison of the muscarinic receptor availability in vivo under treatment with these atypical antipsychotics was performed. [123I]IQNB SPECT scans were obtained in seven subjects treated with a high dose (20 mg) of olanzapine and seven subjects treated with a moderate dose (mean 275.0 mg, range 200-450 mg) of clozapine. Muscarinic receptor-binding indices were determined for basal ganglia, cortex, thalamus and pons. When comparing moderate-dose clozapine with high-dose olanzapine, significantly lower muscarinic receptor availability was found for clozapine in all four cortical regions of interest. Our results suggest that treatment with clozapine results in a stronger blockade of the muscarinic cholinergic receptors than with olanzapine. These results are compatible with the higher rates of anticholinergic side-effects seen with clozapine in clinical practice.
authors.affiliation: University Hospital Hamburg-Eppendorf, Department of Psychiatry, Hamburg, Germany. traedler@uke.uni-hamburg.de
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Raedler
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000493:pharmacokinetics / Q000627:therapeutic use; D001923:Brain Chemistry / Q000187:drug effects; D003024:Clozapine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D011569:Psychiatric Status Rating Scales; D011813:Quinuclidinyl Benzilate / Q000031:analogs & derivatives; D019275:Radiopharmaceuticals; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy; D012565:Schizophrenic Psychology; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D014150:Antipsychotic Agents; D019275:Radiopharmaceuticals; D011976:Receptors, Muscarinic; D001569:Benzodiazepines; D011813:Quinuclidinyl Benzilate; C040062:3-quinuclidinyl-4-iodobenzilate; D003024:Clozapine; D000077152:Olanzapine