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| Targets |
Devapamil specifically targets the L-type voltage-gated calcium channels (Cav1.2). It binds to a site on the alpha-1 subunit of the channel, which is located at the outer surface of the cell membrane. Unlike some other calcium channel blockers, devapamil blocks the calcium currents (ICa) from the inner side of the membrane in a use-dependent manner. It stabilizes the channel in its inactivated state, preventing the influx of calcium ions into the cell. This reduces cardiac contractility, slows atrioventricular conduction, and dilates blood vessels, leading to antihypertensive and antiarrhythmic effects.
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| ln Vitro |
In vitro, Devapamil is a potent L-type calcium channel blocker. At a concentration of 3 uM, it reduces L-type calcium currents (ICa) to 16.1 +/- 8.6%, 11 +/- 8.9%, and 9.3 +/- 6% of control values. Extracellularly applied quaternary devapamil (qD888) inhibits Sr2+ inward currents (ISr) with an IC₅0 of 90 uM and Na+ inward currents with an IC₅0 of 27 uM. These effects are mainly resting-state-dependent. It does not block calcium currents when applied intracellularly via the patch pipette, suggesting that its binding site is on the extracellular side of the channel.
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| ln Vivo |
Devapamil is a calcium channel blocker with potential therapeutic applications in hypertension, angina, and arrhythmias. However, it is not an approved drug. In animal studies, devapamil reduces blood pressure and heart rate. It is used as a pharmacological tool to study the role of calcium channels in cardiac electrophysiology. The parent compound, verapamil, is an FDA-approved drug. The quaternary derivative of devapamil (qD888) is used in experiments to study the extracellular site of action of phenylalkylamines on L-type calcium channels.
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| Enzyme Assay |
The binding of devapamil to L-type calcium channels can be measured using radioligand binding assays. Cardiac membranes (from rat or pig ventricles) are incubated with a radiolabeled calcium channel antagonist, such as [3H]-devapamil or [3H]-verapamil, in the presence of varying concentrations of unlabeled devapamil (0.1-1000 nM). The reaction is carried out in 50 mM Tris-HCl buffer (pH 7.4) at 25degC for 60-90 min. Bound radioligand is separated by filtration through Whatman GF/B filters. The IC₅0 is calculated from competition curves. The inhibition constant (Ki) can be calculated using the Cheng-Prusoff equation. The binding is highly dependent on temperature and calcium concentration.
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| Cell Assay |
The functional activity of devapamil is assessed by whole-cell patch clamp electrophysiology. Isolated rat ventricular myocytes are placed in a recording chamber and continuously perfused with Tyrode‘s solution. A patch pipette is used to achieve the whole-cell configuration. L-type calcium currents (ICa) are elicited by depolarizing voltage steps from a holding potential of -40 mV to various test potentials (0 to +60 mV). Devapamil (1-100 uM) is applied extracellularly, and the reduction in current amplitude is recorded. The IC₅0 for inhibition of ICa is determined from the concentration-response curve. Intracellular application via the patch pipette (30 uM) fails to depress ICa, indicating the extracellular site of action.
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| Animal Protocol |
The in vivo cardiovascular effects of devapamil can be evaluated in normotensive or spontaneously hypertensive rats (SHR). Male Sprague-Dawley or SHR rats (250-350 g, n=6-8/group) are anesthetized. The carotid artery is cannulated for blood pressure measurement, and the jugular vein is cannulated for drug administration. Devapamil (0.1-3 mg/kg) is administered intravenously (IV) as a bolus or by continuous infusion. Mean arterial pressure (MAP) and heart rate (HR) are recorded continuously. Devapamil produces a dose-dependent decrease in MAP and a decrease in HR (negative chronotropic effect). The reduction in MAP is due to peripheral vasodilation (reduced systemic vascular resistance). The duration of action is shorter than that of verapamil. The quaternary derivative (qD888) is ineffective in vivo as it does not cross cell membranes.
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| ADME/Pharmacokinetics |
Devapamil (MW 424.58, LogP ~4.5) is a lipophilic small molecule. It is well absorbed following oral administration. It is extensively metabolized in the liver by CYP3A4, primarily via N-demethylation and O-demethylation. The elimination half-life in humans is estimated to be 4-8 hours, similar to verapamil. It is a substrate for P-glycoprotein (P-gp), which limits its oral bioavailability. The plasma protein binding is high (>90%). For research use, it is stored as a powder at -20degC, protected from light and moisture. It is soluble in DMSO (50 mg/mL) and ethanol.
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| Toxicity/Toxicokinetics |
Devapamil has a similar toxicity profile to verapamil. Overdose can cause severe hypotension, bradycardia, atrioventricular block, and cardiac arrest. It is contraindicated in patients with sick sinus syndrome, second- or third-degree AV block, severe hypotension, and cardiogenic shock. Common adverse effects include constipation, dizziness, headache, and peripheral edema. It is a Category C drug for pregnancy. Devapamil is for research use only and is not approved for human use. For handling, use PPE (gloves, lab coat, safety goggles), work in a fume hood, avoid inhalation and skin contact.
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| References | |
| Additional Infomation |
Devapamil is a nitrile compound that functions as an L-type calcium channel blocker. It exhibits vasodilatory, antiarrhythmic, and calcium channel blocking effects. It is a nitrile, aromatic ether, and tertiary amine compound. (See first source for structural formula.)
Devapamil (D 888; Desmethoxyverapamil; CAS# 92302-55-1) is a research-grade L-type calcium channel blocker (phenylalkylamine class). It is not an FDA-approved drug (verapamil is approved). It is used as a pharmacological tool for studying the structure and function of L-type calcium channels, for patch clamp electrophysiology, and for cardiovascular research. For research use only, not for diagnostic or therapeutic applications. Storage: Powder: -20degC for 3 years, 4degC for 2 years; In solvent: -80degC for 1 year, -20degC for 1 month. |
| Molecular Formula |
C26H36N2O3
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|---|---|
| Molecular Weight |
424.58
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| Exact Mass |
424.273
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| CAS # |
92302-55-1
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| PubChem CID |
65832
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| Appearance |
Typically exists as solids at room temperature
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| Density |
1.0±0.1 g/cm3
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| Boiling Point |
567.0±50.0 °C at 760 mmHg
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| Flash Point |
296.7±30.1 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.53
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| LogP |
4.08
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
31
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| Complexity |
560
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)C(CCCN(C)CCC1=CC(=CC=C1)OC)(C#N)C2=CC(=C(C=C2)OC)OC
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| InChi Key |
VMVKIDPOEOLUFS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H36N2O3/c1-20(2)26(19-27,22-11-12-24(30-5)25(18-22)31-6)14-8-15-28(3)16-13-21-9-7-10-23(17-21)29-4/h7,9-12,17-18,20H,8,13-16H2,1-6H3
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| Chemical Name |
2-(3,4-dimethoxyphenyl)-5-[2-(3-methoxyphenyl)ethyl-methylamino]-2-propan-2-ylpentanenitrile
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| Synonyms |
D 888; Desmethoxyverapamil
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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 | 2.3553 mL | 11.7763 mL | 23.5527 mL | |
| 5 mM | 0.4711 mL | 2.3553 mL | 4.7105 mL | |
| 10 mM | 0.2355 mL | 1.1776 mL | 2.3553 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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