| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
| Targets |
IK.ACh ( IC50 = 40.1 μM )
Pirmenol hydrochloride targets voltage-gated sodium channels in cardiac myocytes, blocking them in a use-dependent manner. This sodium channel blockade slows the rate of depolarization (Phase 0 of the cardiac action potential), thereby reducing the conduction velocity in cardiac tissue. The compound also prolongs the effective refractory period and the action potential duration. Pirmenol hydrochloride has Class Ia antiarrhythmic properties, similar to quinidine and procainamide. The compound also has some anticholinergic (muscarinic receptor antagonist) activity, which may contribute to its effects on heart rate and cardiac conduction. |
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| ln Vitro |
Pirmenol (1 μM) hydrochloride inhibits the IK.ACh triggered by carbachol or intracellular loading of GTPg S in in atrial cells[1].
Pirmenol (5 μM) hydrochloride prolongs the final repolarization of the action potentials and depresses the early portion of the plateau in ventricular myocytes[3]. Pirmenol (1 μM) hydrochloride extends the action potential duration at 90% repolarization in atrial muscles and Purkinje fibers[3]. In vitro studies have demonstrated that Pirmenol hydrochloride effectively blocks sodium channels in cardiac myocytes, reducing the maximum rate of depolarization and prolonging the action potential duration. The compound's effects on cardiac conduction and refractoriness have been characterized using isolated cardiac tissue preparations and patch-clamp electrophysiology. Pirmenol hydrochloride also exhibits some anticholinergic activity, which may contribute to its effects on heart rate. The compound's in vitro activity profile is consistent with its classification as a Class Ia antiarrhythmic agent. Detailed IC50 values for sodium channel blockade are available from electrophysiological studies. |
| ln Vivo |
Pirmenol (2.5 and 5 mg/kg, p.o.) hydrochloride is efficient in treating arrhythmias in dogs with ligated coronary arteries who are conscious[4].
Pirmenol (rats) hydrochloride demonstrates LD50s of 359.9 mg/kg (p.o), 23.6 mg/kg (i.v.)[2]. Pirmenol (mice) hydrochloride demonstrates LD50s of 215.5 mg/kg (p.o), 20.8 mg/kg (i.v.)[2]. In vivo studies have demonstrated that Pirmenol hydrochloride is effective in suppressing ventricular arrhythmias, including premature ventricular contractions and ventricular tachycardia. The compound is administered orally or intravenously and produces significant antiarrhythmic effects in both animal models and clinical studies. In clinical trials, Pirmenol hydrochloride has been shown to be effective in reducing the frequency of ventricular arrhythmias in patients with various cardiac conditions. The compound's effects on hemodynamics and cardiac function have also been studied. The drug is typically administered at doses that achieve therapeutic plasma concentrations without significant adverse effects. |
| Enzyme Assay |
The in vitro sodium channel assay for Pirmenol hydrochloride typically involves measuring the compound's effects on sodium currents in isolated cardiac myocytes or in heterologous expression systems using patch-clamp electrophysiology. Cells are voltage-clamped, and sodium currents are elicited by depolarizing voltage steps. The compound is applied at varying concentrations, and the inhibition of peak sodium current is measured. The IC50 for sodium channel blockade is calculated from dose-response curves. Use-dependent block, which is characteristic of Class Ia antiarrhythmics, is assessed by applying repetitive depolarizing pulses. These assays are standard for characterizing sodium channel blocking activity.
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| Cell Assay |
Cellular assays for Pirmenol hydrochloride are typically conducted using isolated cardiac myocytes or cardiac cell lines. Cells are treated with varying concentrations of the compound, and the effects on action potential parameters (maximum rate of depolarization, action potential duration, resting membrane potential) are measured using microelectrode or patch-clamp techniques. The compound's effects on calcium currents and potassium currents may also be assessed. Cell viability assays are performed to ensure that any observed effects are not due to cytotoxicity. These cell-based assays provide detailed information about the compound's electrophysiological effects.
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| Animal Protocol |
Conscious, coronary artery ligated dogs
Oral administration (p.o.) 2.5 and 5 mg/kg In vivo animal studies for Pirmenol hydrochloride are conducted in rodent, dog, or primate models of arrhythmia. Arrhythmias are induced by various methods, including coronary artery ligation, electrical stimulation, or administration of arrhythmogenic agents. The compound is administered orally or intravenously, and its antiarrhythmic effects are assessed by ECG monitoring. The compound's effects on hemodynamic parameters, including blood pressure and heart rate, are also measured. These studies confirm the compound's antiarrhythmic efficacy and help to characterize its dose-response relationship and duration of action. |
| ADME/Pharmacokinetics |
Pirmenol hydrochloride is administered orally or intravenously. The compound is well-absorbed after oral administration, with a bioavailability of approximately 80-90%. The time to peak plasma concentration is about 1-2 hours after oral dosing. Pirmenol hydrochloride is extensively metabolized in the liver, and its elimination half-life is approximately 7-11 hours. The compound is excreted primarily in urine as metabolites. Therapeutic plasma concentrations are typically in the range of 1-3 microg/mL. The compound's pharmacokinetics are influenced by factors such as hepatic function, renal function, and concomitant medications. Dose adjustments may be necessary in patients with hepatic or renal impairment.
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| Toxicity/Toxicokinetics |
The most common adverse effects of Pirmenol hydrochloride include dizziness, headache, nausea, and gastrointestinal disturbances. The compound's anticholinergic properties may cause dry mouth, blurred vision, and constipation. As with other Class Ia antiarrhythmics, Pirmenol hydrochloride has the potential to cause proarrhythmic effects, including the exacerbation of arrhythmias or the induction of new arrhythmias. The compound should be used with caution in patients with pre-existing cardiac conditions, including heart failure and conduction abnormalities. Regular monitoring of ECG and plasma drug concentrations is recommended during therapy.
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| References |
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| Additional Infomation |
Pirmenol hydrochloride is a Class Ia antiarrhythmic agent used for the treatment of ventricular arrhythmias, including premature ventricular contractions and ventricular tachycardia. The compound works by blocking sodium channels in cardiac myocytes, slowing the rate of depolarization and prolonging the effective refractory period. It has a molecular formula of C22H31ClN2O and a molecular weight of approximately 374.95. Pirmenol hydrochloride is available in oral and intravenous formulations and is administered by prescription only. The drug is not recommended for use in patients with certain cardiac conditions and should be used under the supervision of a healthcare professional.
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| Molecular Formula |
C₂₂H₃₁CLN₂O
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|---|---|
| Molecular Weight |
374.95
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| Exact Mass |
374.212
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| Elemental Analysis |
C, 70.47; H, 8.33; Cl, 9.45; N, 7.47; O, 4.27
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| CAS # |
61477-94-9
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| Related CAS # |
Pirmenol; 68252-19-7
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| PubChem CID |
65501
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| Appearance |
White to yellow solid powder
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| Boiling Point |
499.6ºC at 760 mmHg
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| Flash Point |
256ºC
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| LogP |
5.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
26
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| Complexity |
386
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| Defined Atom Stereocenter Count |
2
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| SMILES |
OC(C1=CC=CC=C1)(CCCN2[C@@H](C)CCC[C@H]2C)C3=CC=CC=N3.Cl[H]
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| InChi Key |
HFIHPVIVQSWZBV-ROSXHPEZSA-N
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| InChi Code |
InChI=1S/C22H30N2O.ClH/c1-18-10-8-11-19(2)24(18)17-9-15-22(25,20-12-4-3-5-13-20)21-14-6-7-16-23-21;/h3-7,12-14,16,18-19,25H,8-11,15,17H2,1-2H3;1H/t18-,19+,22?;
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| Chemical Name |
4-[(2S,6R)-2,6-dimethylpiperidin-1-yl]-1-phenyl-1-pyridin-2-ylbutan-1-ol;hydrochloride
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| Synonyms |
Cl-845; Cl 845Cl845; (±)-Pirmenol hydrochloride
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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 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)
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| Solubility (In Vitro) |
H2O: ~100 mg/mL (~266.7 mM)
DMSO: ~66.7 mg/mL (~177.8 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.55 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 20.8 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: ≥ 2.08 mg/mL (5.55 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 20.8 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: ≥ 2.08 mg/mL (5.55 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 | 2.6670 mL | 13.3351 mL | 26.6702 mL | |
| 5 mM | 0.5334 mL | 2.6670 mL | 5.3340 mL | |
| 10 mM | 0.2667 mL | 1.3335 mL | 2.6670 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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