BEHAVIORAL PHARMACOLOGY OF OLANZAPINE - A NOVEL ANTIPSYCHOTIC DRUG

Background: In this paper, we review the behavioral pharmacology of ol anzapine and compare it to its in vitro profile and to clozapine and a number of other antipsychotic agents, and we estimate the likelihood that olanzapine will be an effective and safe antipsychotic with fewer side effects. Method: Since there is no model of schizophrenia, per s e, a battery of behavioral assays was used. Results: Behavioral assays confirmed the in vitro results that olanzapine interacts with dopamin e, serotonin, and muscarinic receptor subtypes. Moreover, olanzapine a ppears to have a clozapine-like atypical profile based on (1) mesolimb ic selectivity, (2) blocking 5-HT receptors at a lower dose than dopam ine receptors, and (3) inhibiting the conditioned avoidance response ( indicative of antipsychotic efficacy) at doses that are lower than tho se required to induce catalepsy (indicative of extrapyramidal side eff ects). Not only is this profile similar to that of clozapine, but olan zapine has other similarities: olanzapine substitutes for clozapine in a drug discrimination assay; like clozapine and unlike ''typical'' an tipsychotics, olanzapine increases responding in a conflict procedure; and olanzapine, like clozapine, reverses changes induced by antagonis ts of the NMDA receptor. Conclusion: On the basis of these findings, w e predict that olanzapine will be an efficacious antipsychotic, active against both positive and negative symptoms, while producing fewer ex trapyramidal symptoms than existing treatments.