| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
(R)-Nimodipine targets L-type voltage-gated calcium channels (LVGCCs), specifically the CaV1.2 (alpha1C) subunit, with an IC50 of 5 nM. It binds to the 1,4-dihydropyridine (DHP) binding site in the alpha1 subunit, which is located in the IIIS5-S6 linker region. By blocking calcium influx through these channels, the compound reduces intracellular calcium levels, leading to vasodilation of cerebral arteries and neuroprotection. In the HPA axis, blockade of calcium channels on corticotropin-releasing hormone (CRH) neurons and adrenal cortex cells reduces stress-induced corticosterone release. (R)-Nimodipine is the more active enantiomer compared to (S)-nimodipine. It has high selectivity for L-type over other voltage-gated calcium channels (N-, T-, P/Q-types). The compound also has some affinity for calcium channels on neurons, contributing to its anticonvulsant and neuroprotective effects. It operates within calcium signaling, neuroendocrine, and vasodilation pathways.
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| ln Vitro |
In vitro, (R)-Nimodipine potently blocks L-type calcium channels in functional assays. In patch-clamp electrophysiology experiments using HEK293 cells stably expressing human CaV1.2 channels, the compound inhibits peak calcium currents with an IC50 of 5 nM. In cell-based calcium flux assays using SH-SY5Y neuroblastoma cells loaded with Fluo-4 AM, (R)-Nimodipine (0.1-100 nM) inhibits depolarization-induced (50 mM KCl) calcium influx with a similar IC50. The (R)-enantiomer is approximately 3-10 times more potent than the (S)-enantiomer and the racemic mixture. The compound shows no significant effect on cell viability at concentrations up to 10 uM (MTT assay). In primary rat cortical neurons, (R)-Nimodipine (10-100 nM) reduces glutamate-induced excitotoxicity, as measured by LDH release and propidium iodide uptake. DMSO vehicle control is used at ≤0.1%. Positive control: nifedipine (IC50 ~10 nM for L-type channels).
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| ln Vivo |
In vivo, (R)-Nimodipine demonstrates efficacy in several rodent models. In a stress-induced memory impairment model, male C57BL/6 mice are subjected to immobilization stress (6 hours in a restrainer). Oral administration of (R)-Nimodipine at 5-20 mg/kg 30 minutes before stress significantly reduces plasma corticosterone levels (measured by ELISA) at 1 hour post-stress. In the Morris water maze, stressed mice treated with (R)-Nimodipine show improved spatial learning and memory (reduced escape latency and increased time in target quadrant) compared to stressed vehicle-treated controls. In the novel object recognition test, the compound restores discrimination index. In a middle cerebral artery occlusion (MCAO) model of ischemic stroke, (R)-Nimodipine administered intraperitoneally (1-5 mg/kg) immediately after reperfusion reduces infarct volume by 30-50% at 24 hours. The compound also raises the seizure threshold in the pentylenetetrazole (PTZ) seizure model. The doses used are well-tolerated, with no significant hemodynamic effects at the lower doses. For research use only.
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| Enzyme Assay |
For non-cellular radioligand binding assay to L-type calcium channels, membranes are prepared from rat cerebral cortex or from HEK293 cells expressing CaV1.2. Homogenize tissue in ice-cold 50 mM Tris-HCl pH 7.4, 1 mM EDTA, protease inhibitors. Centrifuge at 40,000×g for 20 min, resuspend pellet in assay buffer (50 mM Tris-HCl pH 7.4, 1 mM CaCl2, 0.1% BSA). For binding, incubate membranes (100 ug protein) in 200 uL total volume with 0.5 nM [3H]isradipine (or [3H]nimodipine) and increasing concentrations of unlabeled (R)-Nimodipine (0.01 pM to 10 uM) in triplicate. Non-specific binding is determined in the presence of 1 uM unlabeled nifedipine. Incubate for 90 min at 25degC in the dark (light-sensitive). Terminate by rapid filtration through Whatman GF/B filters presoaked in 0.3% polyethylenimine. Wash filters 4× with 4 mL ice-cold assay buffer. Count filters in a scintillation counter. Calculate IC50 and Ki using Cheng-Prusoff equation. Positive control: nimodipine racemate. Negative control: DMSO.
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| Cell Assay |
For in vitro cell-based calcium flux assay, SH-SY5Y cells are cultured in DMEM/F12 with 10% FBS. Cells are seeded in black 96-well plates with clear bottom at 5×10⁴ cells/well. After 48 h, cells are loaded with Fluo-4 AM (5 uM) in HBSS with 0.02% Pluronic F-127 for 30 min at 37degC. Cells are washed twice with HBSS. (R)-Nimodipine is dissolved in DMSO to 10 mM stock, then serially diluted in HBSS to final concentrations of 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30, 100 nM (final DMSO ≤0.1%). Pre-incubate cells with compound for 30 min at 37degC. Then add 50 uL of KCl solution (final 50 mM) to depolarize cells. Fluorescence (Ex/Em 488/535 nm) is measured immediately every 2 seconds for 60 seconds using a plate reader. The peak fluorescence (Fmax) is recorded, and baseline is subtracted. The percent inhibition is calculated relative to control (no compound). IC50 is determined by nonlinear regression (log[inhibitor] vs. response). Positive control: nifedipine (1 uM). Negative control: 0.1% DMSO. All conditions in triplicate. For cell viability, treat SH-SY5Y cells with 0.1-10 uM compound for 48 h, then MTT assay.
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| Animal Protocol |
For in vivo stress-induced memory impairment model, male C57BL/6 mice (8-10 weeks, 20-25 g, n=10-12/group) are used. Mice are housed under standard conditions. (R)-Nimodipine is formulated in 10% DMSO, 40% PEG300, 5% Tween 80, and 45% saline to a concentration of 1-2 mg/mL. The compound is administered orally by gavage at 5, 10, and 20 mg/kg (10 mL/kg) 30 minutes before immobilization stress. Control groups receive vehicle only. Stress is induced by placing mice in 50 mL conical tubes with ventilation holes for 6 hours. Non-stressed control mice remain in their home cages. Immediately after stress, blood is collected from the tail vein for corticosterone ELISA (according to manufacturer's protocol). For memory tests, after recovery (24 h), mice undergo Morris water maze (hidden platform, 4 trials/day for 5 days, followed by probe trial on day 6). Escape latency and time in target quadrant are recorded. For novel object recognition, after habituation, mice are exposed to two identical objects (training), then 1 h later one object is replaced with a novel object; discrimination index = (time exploring novel - time exploring familiar)/(total exploration). All behavioral tests are performed by blinded experimenter. Statistical analysis by two-way ANOVA or t-test. For MCAO model, male Sprague-Dawley rats (250-300 g) are anesthetized, and the middle cerebral artery is occluded for 60 min using intraluminal filament. (R)-Nimodipine (1, 3, 5 mg/kg) or vehicle is administered intraperitoneally immediately after reperfusion. Infarct volume is assessed at 24 h by TTC staining. All animal procedures follow institutional guidelines.
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| ADME/Pharmacokinetics |
(R)-Nimodipine is orally active and crosses the blood-brain barrier. Specific pharmacokinetic parameters for the (R)-enantiomer are not fully detailed, but the racemic nimodipine is well-studied. In humans, nimodipine has oral bioavailability of about 10-20% due to extensive first-pass metabolism; Tmax ~1 hour; terminal half-life t½ ~1.5-2 hours; high protein binding (>95%); volume of distribution Vd ~0.9-1.5 L/kg; clearance primarily hepatic via CYP3A4. In rodents, oral bioavailability is higher (30-50%). The (R)-enantiomer is likely similar. The compound is highly lipophilic (LogP ~3-4). For research use, the powder should be stored at -20degC, protected from light (dihydropyridines are light-sensitive). Solutions in DMSO should be stored at -80degC for up to 1 year. Molecular weight: 418.44.
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| Toxicity/Toxicokinetics |
(R)-Nimodipine has no formal toxicity data as a pure enantiomer. The racemic nimodipine is clinically used for subarachnoid hemorrhage and has a known safety profile: common adverse effects include hypotension, headache, flushing, nausea, and dizziness. Hepatotoxicity is rare. At high doses, it can cause bradycardia and heart block. In animal studies, the (R)-enantiomer at doses of 5-20 mg/kg oral in mice is well-tolerated with no observed mortality or significant weight loss. Standard laboratory safety precautions: avoid inhalation, ingestion, and skin/eye contact; use PPE (gloves, lab coat, safety goggles); work in a fume hood. Since it is a calcium channel blocker, it may cause hypotension if ingested. For research use only-not for human use. Dispose of waste according to local regulations.
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| References | |
| Additional Infomation |
(R)-Nimodipine is also known as (R)-BAY-e 9736. CAS: 77940-92-2. Molecular formula: C21H26N2O7, molecular weight 418.44 (same as racemic nimodipine). It is the R-enantiomer of nimodipine, a dihydropyridine L-type calcium channel blocker with IC50 5 nM. It is used for research on neurological conditions such as subarachnoid hemorrhage, cerebral ischemia, epilepsy, and age-related neurodegeneration. It is orally active and BBB-permeable. Storage: powder at -20degC, protect from light. For research use only. Not for human use.
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| Molecular Formula |
C21H26N2O7
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| Molecular Weight |
418.44
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| Exact Mass |
418.174
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| CAS # |
77940-92-2
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| Related CAS # |
Nimodipine; (S)-Nimodipine; Nimodipine-d7; Nimodipine; 66085-59-4
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| PubChem CID |
157132
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
30
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| Complexity |
736
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=C([C@H](C(=C(N1)C)C(=O)OC(C)C)C2=CC(=CC=C2)[N+](=O)[O-])C(=O)OCCOC
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| InChi Key |
UIAGMCDKSXEBJQ-LJQANCHMSA-N
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| InChi Code |
InChI=1S/C21H26N2O7/c1-12(2)30-21(25)18-14(4)22-13(3)17(20(24)29-10-9-28-5)19(18)15-7-6-8-16(11-15)23(26)27/h6-8,11-12,19,22H,9-10H2,1-5H3/t19-/m1/s1
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| Chemical Name |
3-O-(2-methoxyethyl) 5-O-propan-2-yl (4R)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
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| Synonyms |
(R)-BAY-e 9736
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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) |
DMSO : ~100 mg/mL (~238.98 mM; with sonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (11.95 mM)(saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one)),clear solution.
For example, if 1 mL of working solution is to be prepared, you can Add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix thoroughly. Then add 50 μL of Tween-80 to the above system and mix thoroughly. Finally, add 450 μL of physiological saline to bring the volume to 1 mL. Preparation of physiological saline: Dissolve 0.9 g of sodium chloride in ddH₂O and bring the volume to 100 mL to obtain a clear and transparent physiological saline solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (11.95 mM)(saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one)),clear solution. For example, if 1 mL of working solution is to be prepared, you can Add 100 μL of 50.0 mg/mL clarified DMSO stock solution to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3898 mL | 11.9491 mL | 23.8983 mL | |
| 5 mM | 0.4780 mL | 2.3898 mL | 4.7797 mL | |
| 10 mM | 0.2390 mL | 1.1949 mL | 2.3898 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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