The new generation of antipsychotic drugs: how atypical are they?

The International Journal of Neuropsychopharmacology
Jeffrey M. Goldstein

Abstract

The cardinal feature of traditional neuroleptic drugs is extrapyramidal symptoms (EPS), such as parkinsonism, akathisia, and dystonia. Irrespective of the autonomic nervous system side-effect profile of a specific neuroleptic, the entire class produces EPS. Therefore, EPS and antipsychotic activity were once thought to be inextricably linked. However, with the discovery of clozapine, this concept was no longer defensible. Clozapine produced antipsychotic actions without associated EPS or increases in serum prolactin levels, and the term 'atypical' was coined to differentiate its actions from those of the traditional agents. Later, the definition of atypical was expanded to encompass clozapine's unique clinical spectrum of activity, including its effectiveness in treating some patients unresponsive to traditional neuroleptics. Clozapine thus became the archetype for a new generation of antipsychotic drugs, which now includes quetiapine, olanzapine, risperidone, sertindole, ziprasidone, zotepine and amisulpride. This paper will review the pharmacological actions that contribute to the unique features of clozapine, focusing on receptor profile and activity in animal models used for evaluations of antipsychotic activity and EPS. Si...Continue Reading

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