| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Calcium channel
Norverapamil HCl targets L-type calcium channels and P-glycoprotein (P-gp). As a calcium channel blocker, it inhibits calcium influx through voltage-gated L-type calcium channels, which are involved in cardiac and vascular smooth muscle contraction. As a P-gp inhibitor, it modulates drug efflux, affecting the pharmacokinetics of co-administered drugs. |
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| ln Vitro |
Norverapamil hydrochloride, also known as (±)-norverapamil, is just as efficient as vitamin D in decreasing isoniazid and rifampicin tolerance and killing intracellular Mycobacterium tuberculosis when used alone. Similar is Lapami. Similar serum levels to verapamil can be attained by norverapamil, which can likewise prevent tolerance generated by macrophages [1]. As CYP3A substrates and mechanism-based inhibitors, verapamil and its primary metabolite norverapamil were found to have nonlinear pharmacokinetics in the clinic [3].
In vitro, Norverapamil HCl acts as an L-type calcium channel blocker and P-glycoprotein inhibitor. It has been shown to be as effective as vitamin D in decreasing isoniazid and rifampicin tolerance and killing intracellular Mycobacterium tuberculosis. It also inhibits macrophage-induced drug tolerance, suggesting potential for tuberculosis treatment shortening. |
| ln Vivo |
The primary metabolite of verapamil is norverapamil hydrochloride (9 mg/kg; oral), which has the following values: terminal half-life, AUC, and Cmax: 9.4 hours, 260 ng▯h/ml, and 41.6 ng/mL, respectively. [4].
In vivo activity of Norverapamil HCl has been demonstrated in animal studies. In male Sprague-Dawley rats, oral administration at 9 mg/kg produced a terminal half-life of 9.4 hours, an AUC of 260 ng·h/mL, and a Cmax of 41.6 ng/mL. As the primary metabolite of verapamil, it contributes to the pharmacological effects of verapamil in vivo. |
| Enzyme Assay |
Cell-free assays for Norverapamil HCl are not typically performed for receptor binding, as it acts on ion channels and transporters. However, its interaction with P-glycoprotein can be studied using membrane preparations and radiolabeled substrates to measure inhibition of P-gp-mediated efflux. Calcium channel blocking activity can be assessed using electrophysiological techniques in isolated membrane patches.
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| Cell Assay |
Drug tolerance likely represents an important barrier to tuberculosis treatment shortening. We previously implicated the Mycobacterium tuberculosis efflux pump Rv1258c as mediating macrophage-induced tolerance to rifampicin and intracellular growth. In this study, we infected the human macrophage-like cell line THP-1 with drug-sensitive and drug-resistant M. tuberculosis strains and found that tolerance developed to most antituberculosis drugs, including the newer agents moxifloxacin, PA-824, linezolid, and bedaquiline. Multiple efflux pump inhibitors in clinical use for other indications reversed tolerance to isoniazid and rifampicin and slowed intracellular growth. Moreover, verapamil reduced tolerance to bedaquiline and moxifloxacin. Verapamil's R isomer and its metabolite norverapamil have substantially less calcium channel blocking activity yet were similarly active as verapamil at inhibiting macrophage-induced drug tolerance. Our finding that verapamil inhibits intracellular M. tuberculosis growth and tolerance suggests its potential for treatment shortening. Norverapamil, R-verapamil, and potentially other derivatives present attractive alternatives that may have improved tolerability[1].
In vitro cellular assays for Norverapamil HCl are performed using cell lines expressing L-type calcium channels or P-glycoprotein. Calcium channel blocking activity is assessed by measuring calcium influx using fluorescent calcium indicators. P-gp inhibitory activity is evaluated by measuring the accumulation of fluorescent P-gp substrates in drug-resistant cell lines. |
| Animal Protocol |
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat [3]
Doses: 9 mg/kg (pharmacokinetic/PK/PK study) Route of Administration: Oral Experimental Results: t1/2=9.4 hrs (hrs (hours)); AUC=260 ng·h/ml; Cmax =41.6ng/ml. In vivo animal studies for Norverapamil HCl are conducted in rodent models to assess its pharmacokinetic properties and pharmacological effects. Studies typically involve oral administration followed by blood sampling to determine pharmacokinetic parameters such as half-life, AUC, and Cmax. The compound's effects on cardiovascular function and drug interactions are also evaluated. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Norverapamil HCl are characterized by its role as the major active metabolite of verapamil. In male SD rats, oral administration at 9 mg/kg resulted in a terminal half-life of 9.4 hours, AUC of 260 ng·h/mL, and Cmax of 41.6 ng/mL. Verapamil and its primary metabolite norverapamil exhibit nonlinear pharmacokinetics due to mechanism-based inhibition of CYP3A.
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| Toxicity/Toxicokinetics |
Toxicology studies of Norverapamil HCl are related to its parent compound verapamil. As a calcium channel blocker, it can cause cardiovascular effects including hypotension and bradycardia. The compound's safety profile is established through its use as a metabolite of verapamil, a widely used clinical drug. Standard safety precautions apply for research use.
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| References |
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| Additional Infomation |
Norverapamil HCl (CAS: 67812-42-4) is the N-desmethyl metabolite of verapamil, an L-type calcium channel blocker and P-glycoprotein inhibitor. It is used in research to study cardiovascular pharmacology, drug metabolism, and multidrug resistance. The compound has a molecular weight of 477.04 g/mol and is for research use only, not for human therapeutic use.
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| Molecular Formula |
C26H37CLN2O4
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|---|---|
| Molecular Weight |
477.04
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| Exact Mass |
476.244185
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| Elemental Analysis |
C, 65.46; H, 7.82; Cl, 7.43; N, 5.87; O, 13.42
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| CAS # |
67812-42-4
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| Related CAS # |
Norverapamil;67018-85-3
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| PubChem CID |
155002
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| Appearance |
Typically exists as white to off-white solids at room temperature
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| Melting Point |
155-160℃ dec.
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| LogP |
2.024
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
33
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| Complexity |
577
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N#CC(C(C)C)(CCCNCCC1=CC=C(OC)C(OC)=C1)C2=CC=C(OC)C(OC)=C2.[H]Cl
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| InChi Key |
OEAFTRIDBHSJDC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H36N2O4.ClH/c1-19(2)26(18-27,21-9-11-23(30-4)25(17-21)32-6)13-7-14-28-15-12-20-8-10-22(29-3)24(16-20)31-5;/h8-11,16-17,19,28H,7,12-15H2,1-6H3;1H
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| Chemical Name |
2-(3,4-Dimethoxyphenyl)-5-[2-(3,4-dimethoxyphenyl)ethylamino]-2-propan-2-ylpentanenitrile hydrochloride
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| Synonyms |
Norverapamil HCl; Norverapamil hydrochloride; Norverapamil hydrochloride; Norverapamil, Hydrochloride; Nor Verapamil Hydrochloride; Norverapamil (hydrochloride); Norverapamil HCl; 2-(3,4-dimethoxyphenyl)-5-[2-(3,4-dimethoxyphenyl)ethylamino]-2-propan-2-ylpentanenitrile hydrochloride; 2-(3,4-dimethoxyphenyl)-5-[2-(3,4-dimethoxyphenyl)ethylamino]-2-propan-2-ylpentanenitrile;hydrochloride;
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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: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
H2O : ≥ 50 mg/mL (~104.81 mM)
DMSO : ≥ 31 mg/mL (~64.98 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.24 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.24 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0963 mL | 10.4813 mL | 20.9626 mL | |
| 5 mM | 0.4193 mL | 2.0963 mL | 4.1925 mL | |
| 10 mM | 0.2096 mL | 1.0481 mL | 2.0963 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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