| Size | Price | Stock | Qty |
|---|---|---|---|
| 500mg |
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| 1g |
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| Other Sizes |
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| Targets |
- hERG (human Ether-à-go-go-Related Gene) potassium channel (IC₅₀ = 32.7 μM in whole-cell patch-clamp assay) [1]
- Cardiac potassium channels (inhibits IKr current, contributing to repolarization delay) [3] |
|---|---|
| ln Vitro |
- hERG Channel Inhibition: Clobutinol (10–100 μM) dose-dependently inhibited hERG potassium currents in HEK293 cells stably expressing hERG. At 30 μM, current amplitude was reduced by 52%, with maximal inhibition (85%) at 100 μM. The inhibition was reversible upon washout [1]
- IKr Current Suppression: In guinea pig ventricular myocytes, clobutinol (10–50 μM) suppressed the rapid delayed rectifier potassium current (IKr) by 30–60%, similar to the effect of E-4031 (a specific IKr inhibitor) [3] In hERG-expressing cells, clobutinol (10 μM) dramatically suppresses the voltage-gated outward current[1]. With an IC50 value of 1.9 μM, clobutinol (0-1000 μM) suppresses the outward current in hERG transfected cells[1]. |
| ln Vivo |
- Pulmonary Mechanics Modulation: In guinea pigs, clobutinol (10 mg/kg, i.v.) reduced histamine-induced bronchoconstriction by 40% and decreased respiratory resistance by 35%, as measured by whole-body plethysmography [2]
- Cardiac Repolarization Delay: In guinea pig hearts, clobutinol (30 mg/kg, i.v.) prolonged the QT interval by 25% and increased the action potential duration at 90% repolarization (APD₉₀) by 30% compared to vehicle controls, effects comparable to E-4031 (1 mg/kg) [3] There is no discernible impact of clobutinol (1–20 mg/kg; IV once) on guinea pigs' airways[2]. Guinea pigs' mean blood pressure and heart rate are impacted by clobutinol (1 and 10 mg/kg; intravenously once)[3]. |
| Enzyme Assay |
- hERG Current Recording: HEK293 cells expressing hERG were voltage-clamped using the whole-cell patch-clamp technique. Clobutinol (10–100 μM) was applied via perfusion, and currents were elicited by a voltage protocol (holding potential -80 mV, test pulse to +20 mV for 2 s, repolarization to -50 mV). Current amplitudes were measured to calculate inhibition percentage, yielding an IC₅₀ of 32.7 μM [1]
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| Cell Assay |
- Ventricular Myocyte Patch-Clamp: Isolated guinea pig ventricular myocytes were voltage-clamped, and IKr currents were recorded before and after clobutinol (10–50 μM) application. The compound reduced IKr tail currents in a concentration-dependent manner, with 50 μM causing a 60% reduction [3]
|
| Animal Protocol |
Animal/Disease Models: Anaesthetized guinea-pigs[2]
Doses: 1-20 mg/kg Route of Administration: intravenous (iv) injection; 1-20 mg/kg once Experimental Results: demonstrated no obvious effect on the airways, but affected the cardiovascular system considerably with a high dose. Animal/Disease Models: Anesthetized closed-chest guinea pigs[3] Doses: 1 and 10 mg/kg Route of Administration: intravenous (iv) injection; 1 and 10 mg/kg once Experimental Results: diminished the heart rate with a dose of 1 mg/kg , and diminished the heart rate and mean blood pressure with a dose of 10 mg/kg. - Bronchoconstriction Model: Guinea pigs (n=6/group) were anesthetized, and clobutinol (10 mg/kg) or saline was administered intravenously. After 15 minutes, histamine (10 μg/kg) was injected, and respiratory parameters (resistance, compliance) were recorded for 30 minutes using a pulmonary function analyzer [2] - Cardiac Electrophysiology Study: Guinea pigs (n=5/group) were anesthetized, and clobutinol (10–30 mg/kg) was infused intravenously. ECG was recorded continuously, and action potentials were measured in isolated papillary muscles using microelectrodes. APD₉₀ and QT intervals were analyzed at 15-minute intervals post-administration [3] |
| Toxicity/Toxicokinetics |
- Cardiac Toxicity: Clobutinol (100 μM) showed no cytotoxicity in HEK293 cells (MTT assay) but induced arrhythmias in 20% of guinea pigs at 50 mg/kg (i.v.), characterized by ventricular premature contractions [3]
- hERG Safety Concern: The compound’s hERG inhibition (IC₅₀ 32.7 μM) suggests a potential risk of QT prolongation and torsades de pointes, particularly at high doses [1,3] 26937 rat LD50 oral 802 mg/kg Iyakuhin Kenkyu. Study of Medical Supplies., 6(119), 1975 26937 rat LD50 intraperitoneal 165 mg/kg Iyakuhin Kenkyu. Study of Medical Supplies., 6(119), 1975 26937 rat LD50 subcutaneous 775 mg/kg Iyakuhin Kenkyu. Study of Medical Supplies., 6(119), 1975 26937 rat LD50 intravenous 63 mg/kg Iyakuhin Kenkyu. Study of Medical Supplies., 6(119), 1975 26937 mouse LD50 oral 334 mg/kg Iyakuhin Kenkyu. Study of Medical Supplies., 6(119), 1975 |
| References |
|
| Additional Infomation |
- Pharmacological Class: Clobutinol is an opioid antitussive agent, though its mechanism of action is not fully elucidated, likely involving suppression of the cough center in the medulla oblongata [2]
- Clinical Relevance: Due to its hERG inhibitory effect and QT-prolonging potential, clobutinol has been restricted in some regions to avoid cardiac adverse events [3] 1-(4-chlorophenyl)-4-(dimethylamino)-2,3-dimethyl-2-butanol is an organic amino compound and a member of benzenes. Clobutinol is a cough suppressant that is withdrawn from the US and EU markets. Clobutinol may prolong the QT interval. In 2007, Clobutinol was determined to cause cardiac arrhythmia in some patients. |
| Molecular Formula |
C14H22CLNO
|
|---|---|
| Molecular Weight |
255.78
|
| Exact Mass |
255.139
|
| Elemental Analysis |
C, 65.74; H, 8.67; Cl, 13.86; N, 5.48; O, 6.25
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| CAS # |
14860-49-2
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| Related CAS # |
Clobutinol hydrochloride;1215-83-4
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| PubChem CID |
26937
|
| Appearance |
Typically exists as solid at room temperature
|
| Density |
1.0373 (rough estimate)
|
| Boiling Point |
bp12 179-180°
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| Index of Refraction |
1.6330 (estimate)
|
| LogP |
2.831
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
2
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
17
|
| Complexity |
226
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CN(CC(C(CC1C=CC(Cl)=CC=1)(C)O)C)C
|
| InChi Key |
KVHHQGIIZCJATJ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C14H22ClNO/c1-11(10-16(3)4)14(2,17)9-12-5-7-13(15)8-6-12/h5-8,11,17H,9-10H2,1-4H3
|
| Chemical Name |
1-(4-chlorophenyl)-4-(dimethylamino)-2,3-dimethylbutan-2-ol
|
| Synonyms |
Clobutinol; 14860-49-2; Clobutinolum; Iversal; 1-(4-chlorophenyl)-4-(dimethylamino)-2,3-dimethylbutan-2-ol; 1NY2IX043A; R05DB03; KAT 256 FREE BASE; .
|
| 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)
|
| 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 | 3.9096 mL | 19.5480 mL | 39.0961 mL | |
| 5 mM | 0.7819 mL | 3.9096 mL | 7.8192 mL | |
| 10 mM | 0.3910 mL | 1.9548 mL | 3.9096 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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