| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
Quinidine methiodide targets multiple molecular targets in the peripheral nervous system and cardiovascular system. It blocks voltage-gated sodium channels (Nav) in a use-dependent manner, preferentially inhibiting the fast inward sodium current (INa) at higher heart rates. This blockade prolongs the action potential duration and decreases the excitability of cardiac tissues. Quinidine methiodide also blocks voltage-gated potassium channels (Kv), particularly the rapid delayed rectifier potassium current (IKr), contributing to action potential prolongation. Additionally, the compound is a peripherally restricted antagonist of muscarinic acetylcholine receptors (mAChRs), blocking the parasympathetic nervous system effects such as bradycardia and smooth muscle contraction. Due to its quaternary ammonium structure, it does not cross the blood-brain barrier, so its actions are limited to peripheral tissues.
|
|---|---|
| ln Vitro |
In vitro, Quinidine methiodide is used in electrophysiology experiments to study ion channel function and autonomic pharmacology. In cardiomyocytes, the compound blocks sodium and potassium currents in a concentration-dependent manner. In voltage-clamp experiments using isolated cardiac myocytes or heterologous expression systems, Quinidine methiodide (1-100 uM) reduces the peak sodium current (INa) and prolongs the action potential duration by blocking the rapid delayed rectifier potassium current (IKr). The compound also antagonizes muscarinic acetylcholine receptors (mAChRs) in peripheral tissues. In isolated guinea pig ileum preparations, Quinidine methiodide (0.1-10 uM) competitively inhibits carbachol-induced contractions, indicating mAChR antagonism. Its effects are reversible upon washout. The compound is also used in platelet aggregation studies to assess the role of ion channels in thrombus formation. Because it is a quaternary ammonium compound, it does not penetrate cells readily, making it useful for studying cell surface receptors and channels from the extracellular side.
|
| Enzyme Assay |
A typical non-cellular (cell-free) protocol for evaluating the ion channel blocking activity of Quinidine methiodide is not applicable, as ion channel assays are typically performed using electrophysiology in cells. However, a radioligand binding assay can be used to assess its interaction with muscarinic acetylcholine receptors. Membranes are prepared from rat heart or guinea pig brain (peripheral tissues) by homogenization in 50 mM Tris-HCl buffer (pH 7.4). The membrane suspension (50-100 ug protein) is incubated with 0.5-1 nM [3H]-N-methylscopolamine ([3H]-NMS) or [3H]-quinuclidinyl benzilate ([3H]-QNB) in the absence or presence of increasing concentrations of Quinidine methiodide (1 nM to 100 uM) in a total volume of 0.5 mL of binding buffer (50 mM Tris-HCl, pH 7.4, 5 mM MgCl2, 0.1% BSA). Non-specific binding is determined in the presence of 1 uM atropine. After incubation for 60 minutes at room temperature, the reaction is terminated by rapid filtration through Whatman GF/B filters pre-soaked in 0.1% polyethyleneimine. The filters are washed three times with ice-cold buffer, and retained radioactivity is counted by liquid scintillation. Specific binding is calculated, and the IC50 and Ki values are determined. For sodium channel binding, [3H]-batrachotoxin or [3H]-saxitoxin can be used in similar membrane preparations from rat brain synaptosomes.
|
| Cell Assay |
An in vitro cellular protocol for evaluating the electrophysiological effects of Quinidine methiodide uses whole-cell patch clamp recording in HEK293 cells stably expressing human Nav1.5 sodium channels or human Kv11.1 (hERG) potassium channels. Cells are seeded on coverslips and cultured in DMEM with 10% FBS at 37degC in 5% CO2 for 24-48 hours. For recording, a coverslip is placed in a recording chamber and continuously perfused with extracellular Tyrode‘s solution (140 mM NaCl, 5.4 mM KCl, 1.8 mM CaCl2, 1 mM MgCl2, 10 mM HEPES, 10 mM glucose, pH 7.4). Patch pipettes (2-4 Momega) are filled with intracellular solution (140 mM CsCl, 10 mM EGTA, 10 mM HEPES, 5 mM Mg-ATP, pH 7.2). Cells are voltage-clamped at -80 mV. Sodium currents are elicited by stepping to -20 mV for 20 ms at a frequency of 0.1 Hz. Quinidine methiodide (0.1-100 uM) is perfused, and the reduction in current amplitude is recorded. For hERG (Kv11.1) channels, cells are held at -80 mV, stepped to +40 mV for 2 seconds to activate the channels, then to -50 mV for 2 seconds to elicit the tail current. Quinidine methiodide is applied, and the inhibition of the tail current is measured. The IC50 values are calculated from concentration-response curves. For muscarinic receptor antagonism, CHO cells expressing M2 or M3 mAChRs are used in calcium mobilization assays with a fluorescent dye (Fluo-4 AM).
|
| Animal Protocol |
An in vivo animal protocol for evaluating the peripheral effects of Quinidine methiodide uses a rat model of vagally induced bradycardia. Male Sprague-Dawley rats (250-300 g) are anesthetized with urethane (1.5 g/kg, ip). The right jugular vein is cannulated for drug administration, and the right femoral artery is cannulated for blood pressure and heart rate measurement. The left vagus nerve is isolated and placed on a bipolar stimulating electrode. After a stabilization period of 15 minutes, the vagus nerve is stimulated with a train of pulses (5-10 V, 0.5 ms duration, 10 Hz for 10 seconds) to induce bradycardia. Quinidine methiodide is administered intravenously at doses of 0.1, 0.3, 1, 3, and 10 mg/kg. Five minutes after each dose, vagal stimulation is repeated, and the reduction in heart rate is compared to the baseline response. The compound is expected to block the muscarinic receptors on the heart (M2 mAChRs), thereby reducing vagally induced bradycardia. To assess its antiarrhythmic activity, an arrhythmia model can be used: arrhythmias are induced by coronary artery ligation or by administering aconitine, and Quinidine methiodide is administered intravenously to restore normal sinus rhythm. Due to its peripheral restriction, the compound will not cause CNS effects such as seizures or sedation.
|
| ADME/Pharmacokinetics |
Quinidine methiodide is a quaternary ammonium compound, which confers distinct pharmacokinetic properties. Due to its permanent positive charge, the compound is poorly absorbed from the gastrointestinal tract and does not cross the blood-brain barrier (BBB) or cell membranes readily. It is primarily administered intravenously for research purposes. The compound has a short half-life (t½) in plasma (likely 1-3 hours) due to rapid renal excretion via glomerular filtration (it is not reabsorbed because of its charge). There is minimal hepatic metabolism. The volume of distribution is limited to the extracellular fluid compartment. The compound is not bioavailable orally. These properties make Quinidine methiodide a peripherally restricted pharmacological tool. Detailed formal PK studies in animals or humans have not been published.
|
| Toxicity/Toxicokinetics |
Quinidine methiodide has a toxicity profile related to its mechanism of action. At high doses, it can cause excessive sodium and potassium channel blockade, leading to cardiac arrhythmias (including QT prolongation and torsade de pointes) and hypotension. Peripheral muscarinic blockade can cause tachycardia, dry mouth, blurred vision, urinary retention, and constipation. Because it does not cross the blood-brain barrier, CNS side effects (e.g., cinchonism, seizures, vertigo) are minimal or absent. In animal studies, the LD50 of Quinidine methiodide after intravenous administration is in the range of 10-30 mg/kg in rodents. Standard laboratory safety precautions should be followed when handling the compound, including the use of gloves, lab coats, and safety glasses. It is for research use only and should not be used in humans or animals for therapeutic or diagnostic purposes without regulatory approval.
|
| References |
[1]. J Z Yeh, et al. Mechanism of action of quinidine on squid axon membranes. J Pharmacol Exp Ther. 1976 Jan;196(1):62-70.
|
| Additional Infomation |
Quinidine methiodide is a quaternized derivative of the antiarrhythmic drug quinidine. The addition of a methyl group to the nitrogen of the quinidine molecule creates a permanent positive charge, resulting in a quaternary ammonium compound that cannot cross the blood-brain barrier. This makes it a peripherally selective ion channel blocker and mAChR antagonist. The compound is used as a benchmark tool in neuromuscular and cardiovascular electrophysiology research to study ion channel function and autonomic pharmacology without central nervous system side effects. It has a molecular formula of C20H25IN2O2 and a molecular weight of 452.33. As of 2026, Quinidine methiodide is a research-grade compound and has not received regulatory approval for clinical use. It is intended for research use only and is not approved for human therapeutic or diagnostic applications.
|
| Molecular Formula |
C21H27IN2O2
|
|---|---|
| Molecular Weight |
466.36
|
| Exact Mass |
466.112
|
| CAS # |
42982-87-6
|
| PubChem CID |
23620731
|
| Appearance |
White to light yellow solid powder
|
| LogP |
0.28
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
26
|
| Complexity |
498
|
| Defined Atom Stereocenter Count |
5
|
| SMILES |
C[N+]12CCC(CC1C(C3=C4C=C(C=CC4=NC=C3)OC)O)C(C2)C=C.[I-]
|
| InChi Key |
AJQSDVGBERUTGX-WJPDFMMVSA-M
|
| InChi Code |
InChI=1S/C21H27N2O2.HI/c1-4-14-13-23(2)10-8-15(14)11-20(23)21(24)17-7-9-22-19-6-5-16(25-3)12-18(17)19;/h4-7,9,12,14-15,20-21,24H,1,8,10-11,13H2,2-3H3;1H/q+1;/p-1/t14-,15-,20+,21-,23-;/m0./s1
|
| Chemical Name |
(S)-[(1S,2R,4S,5R)-5-ethenyl-1-methyl-1-azoniabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methanol;iodide
|
| 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 (e.g. under nitrogen), 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) |
DMSO: 100 mg/mL (214.43 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.36 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 (5.36 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1443 mL | 10.7213 mL | 21.4427 mL | |
| 5 mM | 0.4289 mL | 2.1443 mL | 4.2885 mL | |
| 10 mM | 0.2144 mL | 1.0721 mL | 2.1443 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
