| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| Other Sizes |
| Targets |
Verapamil inhibits L‑type calcium channels (Caᵥ1.2) in cardiac myocytes and vascular smooth muscle cells, thereby reducing calcium influx and decreasing myocardial contractility and vascular tone. It is also a potent first‑generation P‑glycoprotein (P‑gp) inhibitor and inhibits the cytochrome P450 enzyme CYP3A4. These additional targets make verapamil an important tool for studying drug transport and metabolism.
|
|---|---|
| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as tracers for quantification throughout the drug development process. Due to its potential to alter the pharmacokinetic and metabolic characteristics of medications, deuteration has drawn attention[1].
Verapamil‑d3 exhibits the same in vitro profile as non‑labeled verapamil. In isolated rabbit aorta strips, verapamil (0.1‑30 uM) inhibits potassium‑induced contractions in a concentration‑dependent manner. In cell lines over‑expressing P‑gp, verapamil increases the intracellular accumulation of P‑gp substrates, such as rhodamine 123, by blocking drug efflux. |
| ln Vivo |
In anesthetized dogs and rats, intravenous verapamil produces dose‑dependent decreases in mean arterial blood pressure, heart rate, and atrioventricular conduction velocity. The compound also inhibits the outward transport of co‑administered P‑gp substrates from brain tissue, thereby increasing their central nervous system exposure. The deuterated version is not used as a therapeutic but as a tracer.
|
| Enzyme Assay |
A radioligand binding assay using [3H]‑nitrendipine and rat cortical membrane preparations is performed. Membrane homogenates are incubated with the radioligand and increasing concentrations of verapamil‑d3 (0.1 nM‑100 uM) in 50 mM Tris‑HCl buffer (pH 7.4) for 60 minutes at 25degC. Non‑specific binding is determined in the presence of 1 uM nifedipine. Bound radioactivity is separated by filtration and counted.
|
| Cell Assay |
For P‑gp inhibition assays, cells (e.g., Caco‑2 or MDCK‑MDR1) are grown on transwell filters to form confluent monolayers. The fluorescent P‑gp substrate rhodamine 123 (10 uM) is added to the apical side, with or without verapamil‑d3 (1‑100 uM). After 1‑2 hours, the amount of rhodamine that has moved to the basal side is measured fluorometrically. Alternatively, intracellular accumulation of calcein‑AM is assessed.
|
| Animal Protocol |
Male Sprague‑Dawley rats (200‑250 g) are given a single oral (10 mg/kg) or intravenous (1 mg/kg) dose of verapamil hydrochloride. Serial blood samples are collected via a jugular vein catheter at 0, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours post‑dose. Plasma concentrations are analyzed by LC‑MS/MS using verapamil‑d3 as the internal standard. Pharmacokinetic parameters are calculated by non‑compartmental analysis.
|
| ADME/Pharmacokinetics |
Verapamil has an oral bioavailability of approximately 20‑35% due to extensive first‑pass metabolism by CYP3A4. The drug is highly protein‑bound (≈90%). The major metabolite, norverapamil, is also active and accumulates during chronic therapy. The terminal elimination half‑life is 4‑12 hours, depending on the dosing regimen and formulation. The deuterated version has identical pharmacokinetic properties but is used at trace levels.
|
| Toxicity/Toxicokinetics |
Verapamil is generally well‑tolerated but can cause dose‑related side effects, including constipation (most common), bradycardia, atrioventricular block, hypotension, and peripheral edema. Chronic use may lead to gingival hyperplasia or hepatotoxicity. The deuterated version is not administered to humans.
|
| References |
[1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216.
[2]. Gowarty JL, et al. Verapamil as a culprit of palbociclib toxicity. J Oncol Pharm Pract. 2019 Apr;25(3):743-746. [3]. Krikler DM. Verapamil in arrhythmia. Br J Clin Pharmacol. 1986;21 Suppl 2:183S-189S. [4]. Zhou P, et al. Anti-arrhythmic effect of Verapamil is accompanied by preservation of cx43 protein in rat heart. PLoS One. 2013 Aug 12;8(8):e71567. [5]. Rehnqvist N,et al. Effects of metoprolol vs verapamil in patients with stable angina pectoris. The Angina Prognosis Study in Stockholm (APSIS). Eur Heart J. 1996 Jan;17(1):76-81. [6]. Kubo Y, et al. Blood-to-Retina Transport of Fluorescence-Labeled Verapamil at the Blood-Retinal Barrier. Pharm Res. 2018 Mar 12;35(5):93. |
| Additional Infomation |
Verapamil was approved by the FDA in 1981 and has been widely used for the treatment of hypertension, angina pectoris, and supraventricular tachyarrhythmias. Its role as a P‑gp and CYP3A4 inhibitor also makes it useful in preclinical cancer research for overcoming multidrug resistance. The deuterium‑labeled version is a routine internal standard in HPLC‑MS/MS clinical assays.
|
| Molecular Formula |
C27H36D3CLN2O4
|
|---|---|
| Related CAS # |
Verapamil hydrochloride;152-11-4
|
| Appearance |
Typically exists as solid at room temperature
|
| HS Tariff Code |
2934.99.9001
|
| 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, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| 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
|
|---|---|
| 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
