Behavioral Pharmacology of Olanzapine: A Novel Antipsychotic Drug

Background: In this paper, we review the behavioral pharmacology of olanzapine and compareit to its in vitro profile and to clozapine and a number of other antipsychotic agents, and we estimate thelikelihood that olanzapine will be an effective and safe antipsychotic with fewer side effects.Method: Since there is no model of schizophrenia, per se, a battery of behavioral assays was used.Results: Behavioral assays confirmed the in vitro results that olanzapine interacts with dopamine, serotonin,and muscarinic receptor subtypes. Moreover, olanzapine appears to have a clozapine-like atypicalprofile based on (1) mesolimbic selectivity, (2) blocking 5-HT receptors at a lower dose than dopaminereceptors, and (3) inhibiting the conditioned avoidance response (indicative of antipsychoticefficacy) at doses that are lower than those required to induce catalepsy (indicative of extrapyramidalside effects). Not only is this profile similar to that of clozapine, but olanzapine has other similarities:olanzapine substitutes for clozapine in a drug discrimination assay; like clozapine and unlike "typical"antipsychotics, olanzapine increases responding in a conflict procedure; and olanzapine, like clozapine,reverses changes induced by antagonists of the NMDA receptor. Conclusion: On the basis of thesefindings, we predict that olanzapine will be an efficacious antipsychotic, active against both positiveand negative symptoms, while producing fewer extrapyramidal symptoms than existing treatments.