Olanzapine-d8 is deuterium-labeled Olanzapine. Olanzapine (LY170053) is a selective, orally active monoamine antagonist that binds with high affinity to serotonin H1, 5HT2A/2C, 5HT3, 5HT6 (Ki = 7, 4, 11, 57 and 5 nM, respectively), dopamine D1-4 (Ki = 11-31 nM), muscarinic M1-5 (Ki = 1.9-25 nM) and adrenergic α1 receptors (Ki = 19 nM). Olanzapine is an atypical antipsychotic.

Physicochemical Properties

Molecular Formula	C17H12D8N4S
Molecular Weight	320.48
Exact Mass	320.191
CAS #	1093380-13-2
PubChem CID	135954722
Appearance	Typically exists as solid at room temperature
Density	1.3±0.1 g/cm3
Boiling Point	476.0±55.0 °C at 760 mmHg
Flash Point	241.7±31.5 °C
Vapour Pressure	0.0±1.2 mmHg at 25°C
Index of Refraction	1.709
LogP	2.18
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	1
Heavy Atom Count	22
Complexity	432
Defined Atom Stereocenter Count	0
SMILES	[2H]C1(C(N(C(C(N1C)([2H])[2H])([2H])[2H])C2=NC3=CC=CC=C3NC4=C2C=C(S4)C)([2H])[2H])[2H]
InChi Key	KVWDHTXUZHCGIO-UFBJYANTSA-N
InChi Code	InChI=1S/C17H20N4S/c1-12-11-13-16(21-9-7-20(2)8-10-21)18-14-5-3-4-6-15(14)19-17(13)22-12/h3-6,11,19H,7-10H2,1-2H3/i7D2,8D2,9D2,10D2
Chemical Name	2-methyl-4-(2,2,3,3,5,5,6,6-octadeuterio-4-methylpiperazin-1-yl)-10H-thieno[2,3-b][1,5]benzodiazepine
Synonyms	LY170053-d8
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Studies involving the human use of drugs with labeled deuterium suggest that these compounds may offer some advantages when compared with their nondeuterated counterparts. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs. Deutetrabenazine is the first deuterated drug to receive Food and Drug Administration approval. This deuterated form of the drug tetrabenazine is indicated for the treatment of chorea associated with Huntington's disease as well as tardive dyskinesia. Ongoing clinical trials suggest that a number of other deuterated compounds are being evaluated for the treatment of human diseases and not merely as research tools. [1] Olanzapine and GABAA, benzodiazepines (BZD) has weak binding to β-adrenergic receptors (Ki>10 μM) [2][3]. Olanzapine induces autophagy in human SH-SY5Y neural cell lines[4]. Olanzapine (1-100 μM, serum starvation for 144 hours) has significant anti-autophagy effects on glioblastoma cell lines and glioma stem-like cells. Olanzapine can also enhance the antitumor activity of temozolomide (HY-17364) against glioblastoma cell lines[5]. Olanzapine induces apoptosis and necrosis in glioblastoma cell lines[ 5].
ln Vivo	Olanzapine (0.75, 1.5, and 3 mg/kg) was used to assess body weight and periuterine fat mass, as well as insulin, non-esterified fatty acids, triglycerides, and glucose levels in mice [6].
References	[1]. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-216. [2]. Autophagy inhibition uncovers the neurotoxic action of the antipsychotic drug olanzapine. Autophagy. 2014;10(12):2362-78. [3]. APPROVED AGREED-UPON LABELING. [4]. Olanzapine inhibits proliferation, migration and anchorage-independent growth in human glioblastoma cell lines and enhances temozolomide's antiproliferative effect. J Neurooncol. 2015 Mar;122(1):21-33. [5]. Olanzapine for Injection, powder, for solution for intramuscular use. [6]. Chronic administration of olanzapine induces metabolic and food intake alterations: a mousemodel of the atypical antipsychotic-associated adverse effects. Psychopharmacology (Berl). 2006 Jul;186(4):561-71.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.1203 mL	15.6016 mL	31.2032 mL
	5 mM	0.6241 mL	3.1203 mL	6.2406 mL
	10 mM	0.3120 mL	1.5602 mL	3.1203 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.