| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Target: Histamine H1 Receptor (antagonist), Serotonin 5-HT2A Receptor (antagonist). Cyproheptadine is a competitive antagonist of histamine H1 receptors (Ki ~1-2 nM) and serotonin 5-HT2A receptors (Ki ~2-5 nM). It also has moderate anticholinergic activity (muscarinic receptor antagonist) and weak anti-5-HT1 and anti-5-HT2C activity. The deuterated standard is an analytical tracer.
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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].
In vitro, the labeled standard has no direct biological activity. The unlabeled cyproheptadine (0.1-100 nM) inhibits histamine-induced contraction of isolated guinea pig ileum (H1 antagonism) and serotonin-induced platelet aggregation (5-HT2A antagonism). It shows antihistaminic and antiserotonergic potency with IC50 values in the low nanomolar range. It also inhibits calcium influx and reduces cell proliferation in some cancer cell lines. |
| ln Vivo |
In vivo, the unlabeled cyproheptadine is used clinically as an antihistamine for allergic conditions (urticaria, pruritus, angioedema) and as an appetite stimulant in cachexia (due to its antiserotonergic activity blocking serotonin-mediated satiety). It also has off-label use for serotonin syndrome and as a prophylactic for migraine. The deuterated standard is not administered in vivo; it is used as an internal standard for PK studies of cyproheptadine.
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| Enzyme Assay |
For cell-free assays: plasma, serum, or urine samples are spiked with Cyproheptadine-d3 internal standard. After liquid-liquid extraction (e.g., with ethyl acetate or hexane) or solid-phase extraction (SPE), the samples are injected into an LC-MS/MS or GC-MS system. A C18 reverse-phase column and positive ion mode ESI-MS/MS are typically used. Quantitation is based on the analyte/internal standard peak area ratio. Isotope dilution mass spectrometry is used to correct for matrix effects and ensure accurate quantification of cyproheptadine and its metabolites.
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| Cell Assay |
No cell-based assays are performed with the deuterated standard. The unlabeled cyproheptadine is tested in histamine H1 receptor binding assays using cell membranes expressing human H1 receptors. Radioligand binding is performed using 3H-pyrilamine or 3H-mepyramine as the tracer. Competition binding assays are performed to determine Ki values. Functional antagonism is measured by calcium mobilization assays in H1-expressing cells stimulated with histamine, using calcium-sensitive dyes (Fluo-4).
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| Animal Protocol |
No animal studies are conducted with the labeled internal standard itself. For PK studies of cyproheptadine, animals (rats, dogs) are administered the unlabeled drug orally or intravenously. Serial blood samples are collected, plasma is processed, and the deuterated internal standard is used in LC-MS/MS bioanalysis to determine cyproheptadine concentrations. PK parameters (Cmax, Tmax, t1/2, AUC, bioavailability) are calculated. The standard is also used in tissue distribution and metabolism studies.
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| ADME/Pharmacokinetics |
PK properties of cyproheptadine: after oral administration, it is well-absorbed but undergoes extensive first-pass metabolism (oral bioavailability ~30-50%). Tmax is 1-3 h. Plasma protein binding is high (95-98%). It is extensively metabolized by CYP450 enzymes (primarily CYP3A4, CYP2D6) to several active and inactive metabolites, including desmethylcyproheptadine. The terminal elimination half-life is 8-12 h. Excretion occurs mainly via urine and feces. 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. The unlabeled cyproheptadine has a well-characterized safety profile: common adverse effects include drowsiness, sedation, dry mouth, blurred vision, constipation, urinary retention, and increased appetite (which can lead to weight gain). It may cause CNS depression, especially in combination with alcohol or other CNS depressants. The labeled compound is for research use only and not intended for human therapeutic administration. It is non-hazardous for transport under normal laboratory conditions.
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| References | |
| Additional Infomation |
Cyproheptadine-d3 is a research standard and not an active drug substance. The unlabeled cyproheptadine (Periactin) is FDA-approved for the treatment of allergic reactions (urticaria, pruritus) and as an appetite stimulant for weight gain in underweight individuals and cachexia. It is also used off-label for serotonin syndrome, migraine prophylaxis, and cyclic vomiting syndrome. The deuterated standard is used for analytical method development, method validation (AMV), quality control (QC), and abbreviated new drug application (ANDA) submissions for cyproheptadine-containing pharmaceutical products. It is essential for therapeutic drug monitoring and clinical PK studies.
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| Molecular Formula |
C21H21N
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|---|---|
| Molecular Weight |
290.416630506516
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| Exact Mass |
290.186
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| CAS # |
2712455-05-3
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| Related CAS # |
Cyproheptadine;129-03-3
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| PubChem CID |
91971788
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
4.7
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
1
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
22
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| Complexity |
423
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1(C([2H])([2H])[2H])CC/C(=C2\C3C=CC=CC=3C=CC3=CC=CC=C\23)/CC1
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| InChi Key |
JJCFRYNCJDLXIK-FIBGUPNXSA-N
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| InChi Code |
InChI=1S/C21H21N/c1-22-14-12-18(13-15-22)21-19-8-4-2-6-16(19)10-11-17-7-3-5-9-20(17)21/h2-11H,12-15H2,1H3/i1D3
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| Chemical Name |
4-(2-tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,9,11,13-heptaenylidene)-1-(trideuteriomethyl)piperidine
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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 |
| 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4433 mL | 17.2164 mL | 34.4329 mL | |
| 5 mM | 0.6887 mL | 3.4433 mL | 6.8866 mL | |
| 10 mM | 0.3443 mL | 1.7216 mL | 3.4433 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.
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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