Gallopamil
(Synonyms: 戈洛帕米,Methoxyverapamil) 目录号 : GC36105
Gallopamil (Methoxyverapamil) 是一种维拉帕米的甲氧基衍生物 (methoxy derivative of verapamil)，也是一种苯基烷基胺钙 (phenylalkylamine calcium)拮抗剂。Gallopamil 可以作用于血管系统，心脏及其淋巴结构。Gallopamil 以浓度依赖性方式抑制酸分泌，IC50 为 10.9 μM.
Cas No.:16662-47-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Gallopamil (Methoxyverapamil), a methoxy derivative of Verapamil, is a phenylalkylamine calcium antagonist. Gallopamil acts on the vascular system and the heart and nodal structure[1]. Gallopamil inhibits acid secretion in a concentration-dependent manner with an IC50 of 10.9 μM[2]. Ca2+
[1]. Brogden RN, et al. Gallopamil. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in ischaemic heart disease. Drugs. 1994 Jan;47(1):93-115. [2]. Sewing KF, et al. Calcium channel antagonists verapamil and gallopamil are powerful inhibitors of acid secretion in isolated and enriched guinea pig parietal cells. Pharmacology. 1983;27(1):9-14.
| Cas No. | 16662-47-8 | SDF | |
| 别名 | 戈洛帕米,Methoxyverapamil | ||
| Canonical SMILES | COC1=C(OC)C(OC)=CC(C(CCCN(C)CCC2=CC(OC)=C(OC)C=C2)(C#N)C(C)C)=C1 | ||
| 分子式 | C28H40N2O5 | 分子量 | 484.63 |
| 溶解度 | DMSO: 100 mg/mL (206.34 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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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 |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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2.
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Gallopamil. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in ischaemic heart disease
Drugs 1994 Jan;47(1):93-115.PMID:7510624DOI:10.2165/00003495-199447010-00007.
Gallopamil is a methoxy derivative of verapamil. As is typical of the phenylalkylamine class of calcium antagonists, it acts on the vascular system, and on the heart and its nodal structures. In the treatment of stable angina pectoris, Gallopamil is at least as effective as nifedipine and diltiazem, though apparently better tolerated than nifedipine. Typical of calcium antagonists there is little or no tolerance to the antiischaemic effects of Gallopamil. Preliminary studies indicate that Gallopamil, like other calcium antagonists, has cardioprotective potential. However, further investigation is required to explore the clinical relevance of the improved myocardial regional perfusion and free fatty acid utilisation in reversibly ischaemic regions, and the potential of delayed ischaemia during angioplasty that is observed during Gallopamil administration. Gallopamil is well tolerated, exhibiting a low propensity for causing cardiovascular and gastrointestinal adverse effects, thus making it a suitable alternative to other calcium antagonists for the treatment of patients with ischaemic heart disease.
Effect of Gallopamil on excitation-contraction coupling
Gen Pharmacol 1996 Jul;27(5):749-53.PMID:8842675DOI:10.1016/0306-3623(95)02095-0.
1. Investigations performed in skeletal muscle have suggested that phenylalkylamine calcium antagonists, particularly Gallopamil, affect excitation-contraction coupling independently of their effect on the sarcolemmal calcium current. 2. Sarcoplasmic reticulum and single channel studies have provided evidence that phenylalkylamine calcium antagonists inhibit calcium release through the sarcoplasmic reticulum calcium channel/ryanodine receptor. This action has not been observed with dihydropyridine calcium antagonists. 3. Binding experiments have confirmed the existence of intracellular binding sites for phenylalkylamines, and have shown that Gallopamil interferes with the binding of ryanodine to its low affinity sites. 4. The dose-response relationship for the effect of Gallopamil on excitation-contraction coupling has not been definitely established. However, there is evidence that Gallopamil may be effective at concentrations that are close to the therapeutic range.
Gallopamil: cardiovascular scope of action of a highly specific calcium antagonist
J Cardiovasc Pharmacol 1992;20 Suppl 7:S1-10.PMID:1284148DOI:10.1097/00005344-199200207-00002.
According to Fleckenstein's original classification, Gallopamil represents a prototype of highly specific calcium antagonists of Group A. Its large scope of cardiovascular effects is lastly based on one and the same mechanism of action: inhibition of transmembrane calcium influx into myocardial, cardiac pacemaker, and vascular smooth muscle cells. Thereby, in experimental studies that use electrophysiological, biochemical, isotopic, and histological techniques, Gallopamil reduced calcium-dependent myocardial contractility and oxygen consumption; dampened nomotopic and ectopic cardiac pacemaker activity; exerted pronounced vasodilator effects; and protected myocardial cells from calcium overload-induced necrotization. The effects of Gallopamil on myocardium, cardiac pacemakers, and vasculature are quantitatively comparable, surpassing those of verapamil by approximately one order of magnitude. Further clinical studies must demonstrate to what extent humans will benefit from the experimentally proven cardiovascular potential of Gallopamil.
Pharmacokinetics and pharmacodynamics of the enantiomers of Gallopamil
J Pharmacol Exp Ther 1997 Jun;281(3):1102-12.PMID:9190842doi
The pharmacokinetics and pharmacodynamics of the enantiomers of the calcium antagonist Gallopamil have been investigated in six healthy volunteers. Each subject was studied on five occasions after receiving, in randomized order: placebo, 25 mg of (R)-gallopamil, 25 mg of (S)-gallopamil, 50 mg of pseudoracemic [25 mg of deuterated (S)-gallopamil and 25 mg of (R)-gallopamil] and 100 mg of (R)-gallopamil HCl orally. After separate administration, the apparent oral clearances of both enantiomers were similar [(R), 15.1 +/- 9.9 liters/min; (S), 11.0 +/- 6.0 liters/min], indicating that Gallopamil first-pass metabolism is not stereoselective. After coadministration, the apparent oral clearance of each enantiomers decreased [(R), 5.9 +/- 2.8 liters/min; (S), 5.8 +/- 2.66 liters/min], suggesting that a partial saturation of first-pass metabolism occurs because the dose was twice as high than for the single enantiomers. Serum protein binding and renal elimination of Gallopamil are stereoselective, favoring (S)-gallopamil. Analysis of urine samples revealed a marked degree of stereoselectivity in the formation of O- and N-dealkyl metabolites. Because these showed opposite stereoselectivity, canceling out each other, the net result was no or only marginal stereoselectivity. Twenty-five milligrams of (S)-gallopamil prolonged the PR interval in all subjects; however, a greater effect was elicited by 50 mg of (RS)-gallopamil. (R)-Gallopamil (100 mg) did not significantly alter the PR interval, although higher concentrations were attained than after the pseudoracemate. Based on a consideration of (S)-gallopamil serum concentrations, a comparable relationship between (S)-gallopamil level and effect occurred after (S)- and (RS)-gallopamil, indicating that the pharmacological effect produced by the racemate could be totally accounted for by the higher concentrations of (S)-gallopamil attained.
Enantioselective Gallopamil protein binding
Chirality 1993;5(6):414-8.PMID:8398599DOI:10.1002/chir.530050604.
The protein binding of the enantiomers of Gallopamil has been investigated in solutions of human serum albumin, alpha 1-acid glycoprotein and serum. Over the range of concentrations attained after oral Gallopamil administration, the binding of both enantiomers to albumin, alpha 1-acid glycoprotein, and serum proteins was independent of Gallopamil concentration. The binding to both human serum albumin (40 g/liter) [range of fraction bound (fb) R: 0.624 to 0.699; S: 0.502 to 0.605] and alpha 1-acid glycoprotein (0.5 g/liter) (range of fb R: 0.530 to 0.718; S: 0.502 to 0.620) was stereoselective, favoring the (R)-enantiomer (predialysis Gallopamil concentrations 2.5 to 10,000 ng/ml). When the enantiomers (predialysis Gallopamil concentration 10 ng/ml) were studied separately in drug-free serum samples from six healthy volunteers the fraction of (S)-gallopamil bound (fb: 0.943 +/- 0.016) was lower (P < 0.05) than that of (R)-gallopamil (fb: 0.960 +/- 0.010). The serum protein binding of both (R)- and (S)-gallopamil was unaffected by their optical antipodes (fb R: 0.963 +/- 0.011; S: 0.948 +/- 0.015) indicating that at therapeutic concentrations a protein binding enantiomer-enantiomer interaction does not occur. The protein binding of (R)- and (S)-gallopamil ex vivo 2 h after single dose oral administration of 50 mg pseudoracemic Gallopamil (fb R: 0.960 +/- 0.010: predialysis [R] 6.9 to 35.3 ng/ml; S: 0.943 +/- 0.016: predialysis [S] 9.5 to 30.7 ng/ml) was comparable to that observed in vitro in drug-free serum. Gallopamil metabolites formed during first-pass following oral administration, therefore, do not influence the protein binding of (R)- or (S)-gallopamil.