| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Targets (as internal standard): Isotope-Labeled Compounds / 5-HT1A Receptor. The parent compound Gepirone is a selective serotonin 5-HT1A receptor partial agonist, acting presynaptically to reduce serotonin release in the raphe nuclei, thereby enhancing serotonergic neurotransmission in the forebrain, which is associated with mood regulation and anxiety reduction.
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|---|---|
| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1].
No direct in vitro activity is reported for the labeled standard. The unlabeled Gepirone binds to the 5-HT1A receptor with high affinity (Ki values in the low nanomolar range) and exhibits partial agonist activity. It also has some affinity for dopamine D2 receptors, but lower than for 5-HT1A. The labeled compound is analytically inert and used only for quantitation. |
| ln Vivo |
In vivo, the unlabeled Gepirone is orally active and has demonstrated antidepressant and anxiolytic efficacy in animal models such as the forced swim test, tail suspension test, and elevated plus maze. It does not cause significant sedation or cognitive impairment at therapeutic doses. The deuterated standard is not itself administered in vivo for efficacy studies.
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| Enzyme Assay |
For cell-free assay: plasma, serum, or urine samples are spiked with Gepirone-d8 internal standard. After protein precipitation with acetonitrile or methanol, the samples are centrifuged, and the supernatant is injected into an LC-MS/MS system. Quantitation of the analyte (gepirone) is achieved by comparing the analyte peak area to the internal standard peak area.
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| Cell Assay |
No cell-based assays are performed with the deuterated standard. The unlabeled Gepirone is tested in cell lines expressing the human 5-HT1A receptor (e.g., CHO or HEK293 cells). Receptor activation is measured by inhibition of forskolin-stimulated cAMP accumulation via a luminescent or fluorescence-based cAMP assay (e.g., HTRF, AlphaScreen). EC50 values for partial agonism are determined from dose-response curves.
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| Animal Protocol |
No animal studies are conducted with the labeled internal standard. For PK and metabolic studies of Gepirone in animals (rats, dogs), plasma samples are collected after oral or IV administration of the parent drug. The internal standard (Gepirone-d8) is used in LC-MS/MS bioanalysis to accurately quantify the concentration of gepirone and its active metabolites (e.g., 1-pyrimidinylpiperazine, 1-PP).
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| ADME/Pharmacokinetics |
PK properties of parent Gepirone: rapid absorption after oral administration (Tmax 1-2 hours), extensive first-pass metabolism, high plasma protein binding (~95%), and a short elimination half-life (approx. 2-4 hours). It is primarily metabolized by CYP3A4 and CYP2D6 to its active metabolite 1-(2-pyrimidinyl)piperazine (1-PP). The deuterated standard co-elutes with the analyte, ensuring accurate PK parameter determination.
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| Toxicity/Toxicokinetics |
No toxicity data are reported for the deuterated standard. Parent Gepirone has a well-characterized safety profile from clinical trials, including common adverse effects such as dizziness, nausea, headache, and somnolence. Unlike benzodiazepines, it does not cause significant sedation, dependence, or withdrawal. The labeled compound is for research use only and not for human administration.
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| References | |
| Additional Infomation |
Gepirone-d8 is a research standard and is not an active drug substance. It is used for analytical method development, validation (AMV), and quality control (QC) applications for Gepirone. The unlabeled Gepirone has been investigated for major depressive disorder (MDD) and generalized anxiety disorder (GAD) and has received positive opinions from the FDA, though full approval is pending. The labeled compound is an essential tool for bioanalytical method development and clinical pharmacokinetic studies.
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| Exact Mass |
367.282
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|---|---|
| CAS # |
2749331-28-8
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| Related CAS # |
Gepirone;83928-76-1
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| PubChem CID |
163321939
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
26
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| Complexity |
476
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H]C1(C(N(C(C(N1CCCCN2C(=O)CC(CC2=O)(C)C)([2H])[2H])([2H])[2H])C3=NC=CC=N3)([2H])[2H])[2H]
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| InChi Key |
QOIGKGMMAGJZNZ-BGKXKQMNSA-N
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| InChi Code |
InChI=1S/C19H29N5O2/c1-19(2)14-16(25)24(17(26)15-19)9-4-3-8-22-10-12-23(13-11-22)18-20-6-5-7-21-18/h5-7H,3-4,8-15H2,1-2H3/i10D2,11D2,12D2,13D2
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| Chemical Name |
4,4-dimethyl-1-[4-(2,2,3,3,5,5,6,6-octadeuterio-4-pyrimidin-2-ylpiperazin-1-yl)butyl]piperidine-2,6-dione
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| 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
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|---|---|
| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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