olanzapine and 3-quinuclidinyl-4-iodobenzilate

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.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Brain Chemistry; Clozapine; Dose-Response Relationship, Drug; Female; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Quinuclidinyl Benzilate; Radiopharmaceuticals; Receptors, Muscarinic; Schizophrenia; Schizophrenic Psychology; Tomography, Emission-Computed, Single-Photon