An atypical antipsychotic
Olanzapine is a high affinity for 5-HT2 serotonin and D2 dopamine receptor antagonist.
The 5-HT2 serotonin and D2 dopamine receptor s are subfamily of G protein-coupled receptors(GPCRs) [1].
In vitro: Binding studies showed that olanzapine interacted with keyreceptorsof interest in schizophrenia, exihibiting a nanomolar affinity for dopaminergic, serotonergic, alpha 1-adrenergic, and muscarinic receptors [1].
In vivo: Olanzapine was a potent antagonist at DAreceptorsand 5-HT receptors, but showed weaker activity at alpha-adrenergic and muscarinic receptors [1].Administration of Olanzapine at 0.5, 3 and 10 mg/kg (s.c.) increased the extracellulardopamine(DA) and norepinephrine (NE) levels in all three brain areas in a dose-dependent manner.The increases reached peaks 60-90 min after olanzapine administration and lasted for at least 2 h. The highest DA increases in the Acb and Cpu were induced by olanzapine at 3 mg/kg but at 10 mg/kg in the Pfc while the highest NE increase in the Pfc (414% ± 40) induced by 10 mg/kg olanzapine [2].In macaque monkeys, olanzapine treatment resulted in an 8-11% reduction in mean fresh brain weights as well as left cerebrum fresh weights and volumes [3].
参考文献:
[1].?Bymaster FP1,Rasmussen K,Calligaro DO,Nelson DL,DeLapp NW,Wong DT,Moore NA. In vitro and in vivo biochemistry of olanzapine: a novel, atypical antipsychotic drug.J Clin Psychiatry.1997;58Suppl 10:28-36.
[2].?Li XM1,Perry KW,Wong DT,Bymaster FP. Olanzapine increases in vivodopamineand norepinephrine release in rat prefrontal cortex, nucleus accumbens and striatum.Psychopharmacology (Berl).1998 Mar;136(2):153-61.
[3].?Dorph-Petersen KA1,Pierri JN,Perel JM,Sun Z,Sampson AR,Lewis DA. The influence of chronic exposure to antipsychotic medications on brain size before and after tissue fixation: a comparison of haloperidol and olanzapine in macaque monkeys.Neuropsychopharmacology.2005 Sep;30(9):1649-61.
| Cell experiment [1]: | |
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Cell lines |
U87MG and A172 human glioblastoma cell line |
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Preparation method |
The solubility of this compound in DMSO is >15.6mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
IC50: 20–50 μM, 24 h |
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Applications |
Treatment with olanzapine inhibited the proliferation of established glioblastoma cell lines and enhanced the antiproliferative effect of temozolomide on U87MG and A172 cells. Olanzapine (20 μM, 40 μM) inhibited anchorage-independent growth of U87MG cells. Treatment with olanzapine (50 μM, 100 μM) inhibited the migration of A172MG cells. Olanzapine (144 h) exerted proapoptotic and necrotizing effects on glioblastoma cell lines. Olanzapine yielded a significant cytostatic effect on A172 glioblastoma cells. |
| Animal experiment [2]: | |
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Animal models |
Rats |
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Dosage form |
Subcutaneous injection; 0.5 mg/kg, 3 mg/kg and 10 mg/kg |
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Application |
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. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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参考文献: [1]. Karpel-Massler G, Kast R E, Westhoff M A, et al. Olanzapine inhibits proliferation, migration and anchorage-independent growth in human glioblastoma cell lines and enhances temozolomide’s antiproliferative effect[J]. Journal of neuro-oncology, 2015, 122(1): 21-33. [2]. Li X M, Perry K W, Wong D T, et al. Olanzapine increases in vivo dopamine and norepinephrine release in rat prefrontal cortex, nucleus accumbens and striatum[J]. Psychopharmacology, 1998, 136(2): 153-161. |
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