A model of anticholinergic activity of atypical antipsychotic medications

Marci L. Chew, Benoit H. Mulsant, Bruce G. Pollock, Mark E. Lehman, Andrew Greenspan, Margaret A. Kirshner, Robert R. Bies, Shitij Kapur, Georges Gharabawi

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93 Scopus citations


Background: Atypical antipsychotics clozapine, olanzapine, and quetiapine have significant affinity for the muscarinic receptors in vitro, while aripiprazole, risperidone, and ziprasidone do not. Dissimilarity in binding profiles may contribute to the reported differences in the anticholinergic effects of these antipsychotics. However, it is difficult with the available data to predict the likelihood of anticholinergic effects occurring with various doses of an atypical antipsychotic. Methods: We developed a model to assess the potential anticholinergic activity (AA) of atypical antipsychotics at therapeutic doses. A radioreceptor assay was used to measure in vitro AA at 6 clinically relevant concentrations of aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone. Using published pharmacokinetic data, in combination with the measured in vitro AA, dose-AA curves were generated. Results: Clozapine, and to a lesser extent olanzapine and quetiapine showed dose-dependent increases in AA. At therapeutic doses, the AA (in pmol/mL of atropine equivalents) was estimated to range from 27-250, 1-15, and 0-5.4 pmol/mL for clozapine, olanzapine, and quetiapine, respectively. Aripiprazole, risperidone, and ziprasidone did not demonstrate AA at any of the concentrations studied. Conclusions: Therapeutic doses of clozapine, olanzapine, and, to a lesser extent, quetiapine are associated with clinically relevant AA.

Original languageEnglish (US)
Pages (from-to)63-72
Number of pages10
JournalSchizophrenia Research
Issue number1-3
StatePublished - Dec 1 2006
Externally publishedYes


  • Anticholinergic
  • Atypical antipsychotic
  • Cognition
  • Muscarinic receptor
  • Psychopharmacology
  • Schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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  • Cite this

    Chew, M. L., Mulsant, B. H., Pollock, B. G., Lehman, M. E., Greenspan, A., Kirshner, M. A., Bies, R. R., Kapur, S., & Gharabawi, G. (2006). A model of anticholinergic activity of atypical antipsychotic medications. Schizophrenia Research, 88(1-3), 63-72. https://doi.org/10.1016/j.schres.2006.07.011