| In Vitro | In vitro activity: Olanzapine interacts with key receptors of interest in schizophrenia, having a nanomolar affinity for dopaminergic, serotonergic, alpha 1-adrenergic, and muscarinic receptors. Olanzapine has a receptor profile that is similar to that of clozapine: it is relatively nonselective at dopamine receptor subtypes and it shows selectivity for mesolimbic and mesocortical over striatal dopamine tracts (electrophysiology; Fos). |
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| In Vivo | Olanzapine is a potent antagonist at DA receptors (DOPAC levels; pergolide-stimulated increases in plasma corticosterone) and 5-HT receptors (quipazine-stimulated increases in corticosterone), but is weaker at alpha-adrenergic and muscarinic receptors. Olanzapine combined with fluoxetine produces robust, sustained increases of extracellular levels of dopamine ([DA](ex)) and norepinephrine ([NE](ex)) up to 361% and 272% of the baseline in rat prefrontal cortex, respectively, which are significantly greater than either drug alone. Olanzapine at 0.5 mg/kg, 3 mg/kg and 10 mg/kg (s.c.) dose-dependently increases the extracellular dopamine (DA) and norepinephrine (NE) levels in rat prefrontal cortex, nucleus accumbens and striatum. Olanzapine also increases extracellular levels of a DA metabolite, DOPAC, and tissue concentrations of a released DA metabolite, 3-methoxytyramine. Olanzapine results in an 8-11% reduction in mean fresh brain weights as well as left cerebrum fresh weights and volumes in macaque monkeys. Olanzapine results in substantial increases in adiposity: increased total body fat reflecting marked increases in subcutaneous and visceral adipose stores. Olanzapine results in marked hepatic insulin resistance. |
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| Animal model | Macaque monkeys |
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| Formulation & Dosage | 0.5 mg/kg, 3 mg/kg and 10 mg/kg (s.c.) |
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| References | J Clin Psychiatry. 1997;58 Suppl 10:28-36; Neuropsychopharmacology. 2000 Sep;23(3):250-62. |
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