| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| ln Vitro |
Gallopamil inhibited potassium-, acetylcholine-, or adrenaline-induced contraction of isolated major extramural artery systems and peripheral arteries in animal studies. Its vasodilator potency was intermediate between verapamil and nifedipine. The concentration required to relax potassium-induced contracture of isolated canine veins by 50% was 0.02 µmol/L, compared to 2 µmol/L for arteries from the same region. [1]
Gallopamil (0.01 µmol/L to 1 mmol/L) caused dose-related inhibition of superoxide anion production by phorbol myristate acetate-activated neutrophils and inhibited loss of neutrophil filterability induced by platelet-activating factor. However, effective concentrations (4.3 to 9.5 µmol/L) were much higher than therapeutic plasma levels. [1] Gallopamil (250 µmol/L) inhibited adenosine diphosphate- or collagen-induced platelet aggregation in blood from healthy volunteers. [1] In cardiac sarcoplasmic reticulum preparations from bovine ventricular muscle or rat hearts, gallopamil (10–100 nmol/L, within therapeutic range) reduced calcium efflux through calcium channels of the sarcoplasmic reticulum. [1] |
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| ln Vivo |
Intravenous gallopamil (methoxyverapamil; 0.2 mg/kg; for 5 minutes) totally prevents fibrillation (VF) and dramatically lowers ventricular tachycardia (VT). Without appreciably altering heart rate, gallopamil dramatically lowers both the systolic and diastolic blood pressure measured five minutes after injection [3].
In patients with coronary artery disease, oral gallopamil (50mg three times daily or sustained-release 100mg twice daily) reduced resting and exercise-induced heart rate, decreased systolic and diastolic blood pressure by about 5–11% and 9%, respectively, and improved exercise tolerance. It did not significantly affect normal or mildly impaired left ventricular function but improved diastolic function in patients with acute myocardial infarction or hypertrophic cardiomyopathy. [1] Intracoronary administration of gallopamil (1.5 or 3 µg/kg) produced dose-related coronary vasodilation in patients with normal coronary arteries. Intravenous gallopamil (2mg) increased stenosed artery calibre by 26% in patients with coronary artery disease. [1] In animal models, gallopamil administered early after coronary occlusion limited myocardial necrosis size, attenuated creatine phosphokinase and noradrenaline release during reperfusion, maintained mitochondrial function, and reduced ventricular fibrillation and tachycardia following reperfusion. [1] In patients undergoing percutaneous transluminal coronary angioplasty, intracoronary gallopamil (0.4mg) reduced ST-segment and T-wave deviations and lactate release during balloon inflation. [1] |
| Enzyme Assay |
The molecular mechanism of gallopamil in inhibiting calcium transport involves penetration through the sarcolemma and activation of a specific adenosine triphosphatase in the sarcoplasmic reticulum, favoring diastolic calcium influx. It also reduces mitochondrial calcium transport. [1]
Studies using cardiac sarcoplasmic reticulum preparations from bovine ventricular muscle or rat hearts demonstrated that gallopamil, at concentrations between 10 and 100 nmol/L, reduces calcium efflux through the calcium channels of the sarcoplasmic reticulum. This action is shared with verapamil and diltiazem and may contribute to their therapeutic effects. [1] |
| Cell Assay |
In vitro studies showed that gallopamil inhibits superoxide anion production by activated neutrophils and preserves neutrophil filterability, though at supratherapeutic concentrations. [1]
Gallopamil at high concentration (250 µmol/L) inhibited platelet aggregation induced by adenosine diphosphate or collagen in incubated blood from healthy volunteers. [1] |
| Animal Protocol |
Animal/Disease Models: Male Wistar rats, weight 290-370 g [3]
Doses: 0.2 mg/kg Route of Administration: intravenous (iv) (iv)injection; 5 minutes Experimental Results: VT was Dramatically diminished and VF was completely prevented. In open-chested dogs, coronary artery occlusion was induced. Gallopamil (0.08 mg/kg intravenous bolus) was administered 15 minutes after occlusion, followed by a continuous infusion of 0.2 mg/kg/h for 6 hours. This treatment significantly limited the extent of myocardial necrosis compared to untreated controls. [1] In perfused rat hearts, gallopamil was administered before heart isolation or added to the perfusion fluid before induced ischemia. It attenuated creatine phosphokinase and noradrenaline release during reperfusion, maintained mitochondrial function, reduced the rise in diastolic pressure during ischemia, and improved recovery of developed pressure during reperfusion. [1] In closed-chested rats, gallopamil (0.2 mg/kg intravenous) was administered before coronary occlusion. This pretreatment reduced the incidence of ventricular fibrillation and ventricular tachycardia after reperfusion. [1] |
| ADME/Pharmacokinetics |
After oral administration of the regular tablet (50 mg), the mean peak plasma concentration (Cmax) is approximately 30 µg/L, which increases to 68.3 µg/L after repeated administration (50 mg three times daily). The Cmax of the extended-release tablet (100 mg) is 13 µg/L. [1]
Due to extensive first-pass hepatic metabolism, its systemic bioavailability is low (15% after a single dose and approximately 23% after repeated administration). [1] In vitro protein binding is approximately 93%, mainly bound to α1-acid glycoprotein and albumin. Binding is affected by pH. [1] Galopamith is mainly eliminated by metabolism, primarily metabolized to norgalopamith (considered inactive). The mean total plasma clearance after intravenous administration is 66-72 L/h. [1] The terminal elimination half-life of the regular tablet is 2.5-5.5 hours, and that of the extended-release formulation is 5.3-8 hours. [1] After oral administration, 48–55% of the radioactive material is excreted in the urine as metabolites, and 40–50% is excreted in the feces. Only 0.2–2% is excreted unchanged in the urine. [1] In patients with cirrhosis, total plasma clearance is reduced, absolute bioavailability increases to about 60%, and the elimination half-life is prolonged to an average of 11.6 hours, indicating a need for dose reduction. [1] |
| Toxicity/Toxicokinetics |
In a large, short-term, uncontrolled trial involving more than 33,000 patients, gastrointestinal symptoms (nausea, constipation, epigastric pain) occurred in 4.4% to 8.3% of patients. [1] Cardiovascular adverse reactions included orthostatic hypotension, flushing, peripheral edema (2% to 2.4%), bradycardia (0.5%), first- and second-degree atrioventricular block (0.3%), and tachycardia (0.2%). Existing heart failure worsened in 0.03% of patients. [1] Other reported adverse reactions included headache (1.3% to 1.6%), fatigue/asthenia (0.17% to 0.8%), nervousness (0.14%), dry mouth (0.12%), and fever (0.15%). [1] Adverse reactions led to treatment discontinuation in 1.4% to 3% of patients. [1] The in vitro protein binding rate was approximately 93%. [1]
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| References |
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| Additional Infomation |
Gallopamil belongs to the benzene class and organic amino compounds. Gallopamil has been used in clinical trials for the treatment of asthma. It is a coronary vasodilator and an analog of isoprelatrix (verapamil), with an additional methoxy group on the benzene ring. Gallopamil is a methoxy derivative of verapamil, a benzene alkylamine calcium channel blocker. It is used to treat chronic stable angina. The usual oral dose is 50 mg three times a day (regular dose) or 100 mg once or twice a day (suspension-release dose). For unstable or variant angina, 30-60 µg/kg can be injected intravenously, followed by continuous infusion at a rate of 0.3-1 µg/kg/min. The dose should be reduced in patients with cirrhosis. [1] Preliminary studies suggest that the drug may have cardioprotective effects, such as improving local myocardial perfusion and fatty acid utilization in reversibly ischemic areas, and may delay ischemia during angioplasty. [1]
This drug appears to have almost no adverse effects on lipid metabolism, and no significant antianginal tolerance has been observed with long-term use. [1] |
| Molecular Formula |
C28H40N2O5
|
|---|---|
| Molecular Weight |
484.6276
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| Exact Mass |
520.27
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| CAS # |
16662-47-8
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| Related CAS # |
Gallopamil hydrochloride;16662-46-7
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| PubChem CID |
1234
|
| Appearance |
White to off-white solid powder
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| Density |
1.068g/cm3
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| Boiling Point |
605.9ºC at 760mmHg
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| Flash Point |
320.2ºC
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| Vapour Pressure |
1.25E-14mmHg at 25°C
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| Index of Refraction |
1.523
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| LogP |
5.664
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
35
|
| Complexity |
639
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
XQLWNAFCTODIRK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H40N2O5/c1-20(2)28(19-29,22-17-25(33-6)27(35-8)26(18-22)34-7)13-9-14-30(3)15-12-21-10-11-23(31-4)24(16-21)32-5/h10-11,16-18,20H,9,12-15H2,1-8H3
|
| Chemical Name |
5-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]-2-propan-2-yl-2-(3,4,5-trimethoxyphenyl)pentanenitrile
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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 (~206.34 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.16 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 (5.16 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.16 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0634 mL | 10.3171 mL | 20.6343 mL | |
| 5 mM | 0.4127 mL | 2.0634 mL | 4.1269 mL | |
| 10 mM | 0.2063 mL | 1.0317 mL | 2.0634 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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