Olanzapine: a basic science update

Olanzapine, an atypical antipsychotic, has a broad receptor binding profile , which may account for its pharmacological effects in schizophrenia, fn vi tro receptor binding studies showed a high affinity for dopamine D2, D-3 an d D-4 receptors; all 5-HT2 receptor subtypes and the 5-HT6 receptor; muscar inic receptors, especially the M-1 subtype; and alpha(1)-adrenergic recepto rs. tn vivo studies showed that olanzapine had potent activity at D-2 and 5 -HT2A receptors, but much less activity at D-1 and muscarinic receptors, an d that it inhibited dopaminergic neurons in the A10 but not the A9 tract, s uggesting that this agent will not cause extrapyramidal side-effects (EPS). Microdialysis studies showed that olanzapine increased the extracellular l evels of norepinephrine and dopamine, but not 5-HT, in the prefrontal corte x, and increased extracellular dopamine levels in the neostriatum and nucle us accumbens, areas of the brain associated with schizophrenia, Studies of gene expression showed that olanzapine 10 mg/kg also increased Fos expressi on in the prefrontal cortex, the dorsolateral striatum, and the nucleus acc umbens. These findings are consistent with the effectiveness of olanzapine on both negative and positive symptoms and suggest that, with careful dosin g, olanzapine should not cause EPS.