| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Calcium channels (L-type voltage-gated calcium channels). Nicardipine is a dihydropyridine-class calcium channel blocker that binds to the alpha1 subunit of L-type calcium channels, blocking calcium influx through the channel. This results in vasodilation, reduction of peripheral vascular resistance, and lowering of blood pressure. The (R)-enantiomer is the less active isomer, with the (S)-enantiomer contributing more significantly to the pharmacological activity of the racemic drug.
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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 impact on a drug's pharmacokinetics and metabolic profile, it has drawn attention [1].
Nicardipine blocks cardiac calcium channels with an IC50 of 1 uM. The (R)-enantiomer is the less active R-enantiomer of nicardipine, showing lower potency for calcium channel blockade compared to the (S)-enantiomer or the racemate. As a deuterium-labeled internal standard, (R)-Nicardipine-d3 has nearly identical physicochemical properties to the non-deuterated compound but is distinguished by mass spectrometry due to the mass shift, enabling precise quantification. |
| ln Vivo |
As a deuterated internal standard, (R)-Nicardipine-d3 is not intended for in vivo pharmacological activity assessment. The non-deuterated nicardipine (racemate) is a clinically used calcium channel blocker. In vivo, nicardipine acts as an agent for chronic stable angina and for controlling blood pressure (hypertension). It works by relaxing the muscles of the heart and blood vessels, reducing the workload on the heart. The (R)-enantiomer shows less activity than the racemate.
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| Enzyme Assay |
For TSPO binding assays, membrane fractions from rat or human tissues (e.g., brain, adrenal gland) or recombinant TSPO are incubated with the radioligand [3H]-PK11195 (1-2 nM) and varying concentrations of test compound in assay buffer. After incubation at 25degC for 60-90 minutes, bound and free radioligand are separated by rapid filtration through GF/B filters. Radioactivity is counted to calculate Ki values using Cheng-Prusoff equation. ONO-2952 shows Ki values of 0.33-9.30 nM.
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| Cell Assay |
For neuroinflammatory assays, murine BV-2 microglial cells or primary microglia are seeded in 96-well plates and pre-incubated with ONO-2952 (0.1 nM to 1 uM) for 1 hour. Cells are then stimulated with LPS (100 ng/mL) for 6-24 hours. Supernatants are collected, and TNF-alpha, IL-6, and IL-1beta levels are measured by ELISA. Reactive oxygen species (ROS) production is measured using DCFH-DA (2′,7′-dichlorofluorescin diacetate) fluorescent dye. Nitric oxide (NO) production is measured by Griess reagent.
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| Animal Protocol |
For stress-related behavioral studies, rat models of acute stress (restraint stress, forced swim test, elevated plus maze) or chronic social defeat stress (CSDS) in mice are used. ONO-2952 is administered orally (doses 1-30 mg/kg) 30-60 minutes before stress exposure. Behavioral assessments include open field test (anxiety), forced swim test and tail suspension test (depression), and marble burying test (compulsive behavior). Brain tissue is collected for measurement of neurosteroids (allopregnanolone) and noradrenaline by LC-MS/MS or HPLC-ECD.
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| ADME/Pharmacokinetics |
TSPO antagonists including ONO-2952 are orally bioavailable and penetrate the blood-brain barrier (BBB). Brain TSPO occupancy of 50% or more is required for pharmacological effect. In positron emission tomography (PET) studies using [11C]PK11195, ONO-2952 demonstrated dose-dependent occupancy of TSPO in the brains of conscious monkeys. The compound has good metabolic stability and a half-life suitable for once-daily oral dosing. Detailed PK parameters such as Cmax, Tmax, AUC, and t1/2 are not publicly available but are consistent with once-daily oral administration based on literature reports.
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| Toxicity/Toxicokinetics |
In preclinical toxicity studies, ONO-2952 is well-tolerated at effective doses. Because TSPO is involved in steroidogenesis, long-term TSPO antagonism may theoretically affect steroid hormone synthesis, but no significant endocrine adverse effects have been reported in animal studies at therapeutic doses. No significant hepatotoxicity, nephrotoxicity, or cardiotoxicity has been observed. Comprehensive human safety data would be generated during clinical trials, but no Phase 3 results are publicly available for ONO-2952.
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| References | |
| Additional Infomation |
ONO-2952 was developed by Ono Pharmaceutical Co., Ltd. for the treatment of stress-related disorders including generalized anxiety disorder and irritable bowel syndrome (IBS). The compound has been evaluated in Phase 2 clinical trials. A randomized, double-blind, placebo-controlled clinical trial in patients with IBS with diarrhea (IBS-D) was conducted to evaluate the efficacy, safety, and pharmacokinetics of ONO-2952. Results showed that ONO-2952 was well-tolerated and improved abdominal pain/discomfort and bowel habits in IBS-D patients. This product is for research use only.
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| Molecular Formula |
C26H26D3N3O6
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| Molecular Weight |
482.54
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| Related CAS # |
(R)-Nicardipine;76093-35-1
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| Appearance |
White to off-white solid powder
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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 | 2.0724 mL | 10.3618 mL | 20.7237 mL | |
| 5 mM | 0.4145 mL | 2.0724 mL | 4.1447 mL | |
| 10 mM | 0.2072 mL | 1.0362 mL | 2.0724 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.
Products are for research use only; We do not sell to patients
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