Synonym
LY170055; LY 170055; LY-170055; N-desmethyl Olanzapine; N desmethyl Olanzapine; 4'-N-desmethyl Olanzapine;
IUPAC/Chemical Name
2-methyl-4-(piperazin-1-yl)-10H-benzo[b]thieno[2,3-e][1,4]diazepine
InChi Key
FHPIXVHJEIZKJW-UHFFFAOYSA-N
InChi Code
InChI=1S/C16H18N4S/c1-11-10-12-15(20-8-6-17-7-9-20)18-13-4-2-3-5-14(13)19-16(12)21-11/h2-5,10,17,19H,6-9H2,1H3
SMILES Code
CC1=CC2=C(NC3=C(N=C2N4CCNCC4)C=CC=C3)S1
Purity
>95% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
N-desmethyl Olanzapine is a major metabolite of the atypical antipsychotic agent olanzapine.
In vitro activity:
Consistently, in vitro studies indicated that olanzapine increased medium triglyceride levels and decreased medium apoA5 levels in a dose-dependent manner in human HepG2 cells and primary mouse hepatocytes. Whereas the olanzapine treatment increased hepatic apoA5 protein in vitro, without effects on hepatic APOA5 mRNA.
Reference: Front Pharmacol. 2022 Aug 12;13:935362. https://pubmed.ncbi.nlm.nih.gov/36034782/
In vivo activity:
DMO (N-desmethyl-olanzapine) administration (2 mg/kg, i.g.) to high-fat diet induced obesity mice for 4 weeks induced a remarkable loss of body weight and fat mass. DMO improved insulin resistance and energy expenditure in mice, but had no significant effects on dyslipidemia or hepatic steatosis. Moreover, DMO induced morphological changes in the white adipose tissue, accompanied by reduced interleukin-1β (IL-1β) production and increased UCP1 expression.
Reference: Psychoneuroendocrinology. 2019 Oct;108:163-171. https://pubmed.ncbi.nlm.nih.gov/31302499/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
0.0 |
100.53 |
| DMSO |
30.0 |
100.53 |
| DMSO:PBS (pH 7.2) (1:4) |
0.2 |
0.67 |
| Ethanol |
10.0 |
33.51 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
298.41
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Huang PP, Zhu WQ, Xiao JM, Zhang YQ, Li R, Yang Y, Shen L, Luo F, Dai W, Lian PA, Tang YX, Ran JL, Huang XS. Alterations in sorting and secretion of hepatic apoA5 induce hypertriglyceridemia due to short-term use of olanzapine. Front Pharmacol. 2022 Aug 12;13:935362. doi: 10.3389/fphar.2022.935362. PMID: 36034782; PMCID: PMC9411997.
2. Zhang X, Zhao Y, Shao H, Zheng X. Metabolic and endocrinal effects of N-desmethyl-olanzapine in mice with obesity: Implication for olanzapine-associated metabolic changes. Psychoneuroendocrinology. 2019 Oct;108:163-171. doi: 10.1016/j.psyneuen.2019.06.017. Epub 2019 Jul 6. PMID: 31302499.
In vitro protocol:
1. Huang PP, Zhu WQ, Xiao JM, Zhang YQ, Li R, Yang Y, Shen L, Luo F, Dai W, Lian PA, Tang YX, Ran JL, Huang XS. Alterations in sorting and secretion of hepatic apoA5 induce hypertriglyceridemia due to short-term use of olanzapine. Front Pharmacol. 2022 Aug 12;13:935362. doi: 10.3389/fphar.2022.935362. PMID: 36034782; PMCID: PMC9411997.
In vivo protocol:
1. Zhang X, Zhao Y, Shao H, Zheng X. Metabolic and endocrinal effects of N-desmethyl-olanzapine in mice with obesity: Implication for olanzapine-associated metabolic changes. Psychoneuroendocrinology. 2019 Oct;108:163-171. doi: 10.1016/j.psyneuen.2019.06.017. Epub 2019 Jul 6. PMID: 31302499.
1: Lou HG, Ruan ZR, Jiang B, Chen JL. Simultaneous quantification of olanzapine and its metabolite N-desmethylolanzapine in human plasma by liquid chromatography tandem mass spectrometry for therapeutic drug monitoring. Biomed Chromatogr. 2015 May;29(5):671-8. doi: 10.1002/bmc.3329. Epub 2014 Oct 8. PMID: 25297964.
2: Günther KN, Banner J, Linnet K, Johansen SS. Segmental hair analysis of olanzapine and N-desmethyl-olanzapine in postmortem hair from mentally ill patients by LC-MS/MS. J Pharm Biomed Anal. 2020 Oct 25;190:113510. doi: 10.1016/j.jpba.2020.113510. Epub 2020 Aug 2. PMID: 32814260.
3: Zhang X, Zhao Y, Shao H, Zheng X. Metabolic and endocrinal effects of N-desmethyl-olanzapine in mice with obesity: Implication for olanzapine- associated metabolic changes. Psychoneuroendocrinology. 2019 Oct;108:163-171. doi: 10.1016/j.psyneuen.2019.06.017. Epub 2019 Jul 6. PMID: 31302499.
4: Wu TH, Chiu CC, Chen PY, Huang MC, Chen CH, Shen WW, Lu ML. Obsessive- compulsive symptoms in patients with schizophrenia: Relationships with olanzapine pharmacological parameters, psychopathology, and quality of life. Psychiatry Res. 2019 Jun;276:1-5. doi: 10.1016/j.psychres.2019.03.007. Epub 2019 Mar 6. PMID: 30981095.
5: Lu ML, Chen CH, Kuo PT, Lin CH, Wu TH. Application of plasma levels of olanzapine and N-desmethyl-olanzapine to monitor metabolic parameters in patients with schizophrenia. Schizophr Res. 2018 Mar;193:139-145. doi: 10.1016/j.schres.2017.07.022. Epub 2017 Jul 15. PMID: 28720417.
6: Lu ML, Wu YX, Chen CH, Kuo PT, Chen YH, Lin CH, Wu TH. Application of Plasma Levels of Olanzapine and N-Desmethyl-Olanzapine to Monitor Clinical Efficacy in Patients with Schizophrenia. PLoS One. 2016 Feb 5;11(2):e0148539. doi: 10.1371/journal.pone.0148539. PMID: 26849777; PMCID: PMC4746067.
7: Lu ML, Lin CH, Chen YC, Yang HC, Wu TH. Determination of olanzapine and N-desmethyl-olanzapine in plasma using a reversed-phase HPLC coupled with coulochemical detection: correlation of olanzapine or N-desmethyl-olanzapine concentration with metabolic parameters. PLoS One. 2013 May 31;8(5):e65719. doi: 10.1371/journal.pone.0065719. PMID: 23741510; PMCID: PMC3669135.
8: Wiebelhaus JM, Webster KA, Meltzer HY, Porter JH. The metabolites N-desmethylclozapine and N-desmethylolanzapine produce cross-tolerance to the discriminative stimulus of the atypical antipsychotic clozapine in C57BL/6 mice. Behav Pharmacol. 2011 Sep;22(5-6):458-67. doi: 10.1097/FBP.0b013e328348ec4f. PMID: 21712711.
9: Haslemo T, Refsum H, Molden E. The effect of ethinylestradiol-containing contraceptives on the serum concentration of olanzapine and N-desmethyl olanzapine. Br J Clin Pharmacol. 2011 Apr;71(4):611-5. doi: 10.1111/j.1365-2125.2010.03880.x. PMID: 21395655; PMCID: PMC3080651.
10: Josefsson M, Roman M, Skogh E, Dahl ML. Liquid chromatography/tandem mass spectrometry method for determination of olanzapine and N-desmethylolanzapine in human serum and cerebrospinal fluid. J Pharm Biomed Anal. 2010 Nov 2;53(3):576-82. doi: 10.1016/j.jpba.2010.03.040. Epub 2010 Apr 10. PMID: 20452161.
