| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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Arotinolol (Almarl) is a medication acting as a nonselective α/β-adrenergic receptor blocker and a vasodilating β-blocker. It is an antihypertensive medication used to treat both non-cardiovascular and cardiovascular pathologies.
| Targets |
5-HT2A Receptor
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|---|---|
| ln Vitro |
Arotinolol demonstrates the selectivity of β-adrenergic receptors as demonstrated by its binding to rat cerebral cortical membranes with pKi values of 9.74 and 9.26 for β1 and β2 adrenoceptors, respectively, in response to 125I-ICYP. There is equal selectivity between β1 and β2[2].
Arotinolol displaces 125I-ICYP binding to 5HT1B-receptors with the pKi values of 7.97 and 8.16, respectively, for β1 and β2 adrenergic receptors, demonstrating its potency for inhibiting the binding of the same radioligand to the 5HT1B-serotonergic receptor site[2]. |
| ln Vivo |
Arotinolol (oral gavage; 200 mg/kg; 8 weeks) can dramatically lower PWV and CAP. It can also lessen aortic collagen depositions and enhance arterial stiffness in SHR mice[1].
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| Animal Protocol |
SHR mice
200 mg/kg Orally gavage; 200 mg/kg; once daily; 8 weeks |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Alotinol is rapidly absorbed and widely distributed in plasma. Peak plasma concentrations are reached 2 hours after the first dose. The stereoselectivity of alotinol is crucial to its pharmacokinetic profile. Both enantiomers are found in urine, suggesting that urine is its primary route of excretion. Alotinol is detectable in urine 2–4 hours after the first dose. The stereoselectivity of alotinol is crucial to its pharmacokinetic profile. The S-enantiomer is highly retained in erythrocytes. Distribution studies indicate that alotinol is primarily distributed from plasma to the liver, followed by the lungs, and finally the heart. Distribution in the liver is independent of the molecule's stereochemistry. Metabolism/Metabolites The stereoselectivity of alotinol is crucial to its pharmacokinetic profile. The R-enantiomer remains unchanged and is excreted in the urine in this form, while the S-enantiomer is metabolized. Biological half-life According to reports, the half-life of alotinol is 7.2 hours. |
| Toxicity/Toxicokinetics |
Protein Binding
The stereoselectivity of alotinol is crucial to its pharmacokinetic characteristics. Alotinol binds highly to serum proteins, with the R-enantiomer accounting for 95.3% and the S-enantiomer for 84.5% of the initial dose. This stereoselectivity is thought to be related to α1-acid glycoprotein. |
| References | |
| Additional Infomation |
Arotinolol belongs to the thiophene class of aromatic amides. Arotinolol is an α and β receptor blocker developed in Japan. It is a thiopropanolamine containing a tert-butyl group. Its potential as an antihypertensive drug has been studied. Arotinolol was developed by Sumitomo Pharmaceutical Co., Ltd. and is currently undergoing clinical trials.
Drug Indications Arotinolol has been introduced as an antihypertensive drug since 1986. It has also been investigated for other functions, such as controlling tremor in patients with Parkinson's disease, and is currently undergoing clinical trials for controlling blood pressure and heart rate. Mechanism of Action Arotinolol binds to β1, β2, and α1 adrenergic receptors with extremely high affinity. Radioligand studies have shown that Arotinolol has a higher affinity for β receptors than for α receptors. Its mechanism of action appears to be through β receptor blockade to reduce cardiac output and further inhibition of the α receptor blockade-mediated increase in peripheral resistance counterregulation. Pharmacodynamics Preclinical studies have shown that alotinol lacks intrinsic sympathomimetic activity or membrane-binding properties. Alotinol has been shown to possess vasodilatory activity. This property has also been shown to be primarily mediated by its α1-receptor blocking effect. In preclinical trials for hypertension, alotinol exhibited specific acute bradycardia and hypotensive effects, significantly reducing heart rate. Some reports indicate that daily administration of alotinol can delay the onset of hypertension. Alotinol can dose-dependently reduce myocardial contractility and coronary blood flow, and increase total peripheral resistance. Clinical trials have confirmed these effects of alotinol; the drug can lower cardiac indexes, thereby reducing blood pressure. |
| Molecular Formula |
C15H21N3O2S3
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|---|---|
| Molecular Weight |
371.54114
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| Exact Mass |
371.079
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| Elemental Analysis |
C, 48.49; H, 5.70; N, 11.31; O, 8.61; S, 25.89
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| CAS # |
68377-92-4
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| Related CAS # |
87055-50-3 (R-isomer HCl); 68377-92-4; 92075-58-6 (R-isomer); 68377-91-3 (HCl); 101540-26-5 (S-isomer HCl)
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| PubChem CID |
2239
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
599.8±60.0 °C at 760 mmHg
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| Melting Point |
148-149ºC
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| Flash Point |
316.6±32.9 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.646
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| LogP |
2.67
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
23
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| Complexity |
406
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1=CC=C(C2=CSC(SCC(O)CNC(C)(C)C)=N2)S1)N
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| InChi Key |
BHIAIPWSVYSKJS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H21N3O2S3/c1-15(2,3)17-6-9(19)7-21-14-18-10(8-22-14)11-4-5-12(23-11)13(16)20/h4-5,8-9,17,19H,6-7H2,1-3H3,(H2,16,20)
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| Chemical Name |
5-[2-[3-(tert-butylamino)-2-hydroxypropyl]sulfanyl-1,3-thiazol-4-yl]thiophene-2-carboxamide
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| Synonyms |
Arotinolol; Almarl
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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: ~125 mg/mL (~336.4 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.60 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 (5.60 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 (5.60 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 | 2.6915 mL | 13.4575 mL | 26.9150 mL | |
| 5 mM | 0.5383 mL | 2.6915 mL | 5.3830 mL | |
| 10 mM | 0.2692 mL | 1.3458 mL | 2.6915 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01351636 | Completed | Drug: Arotinolol Hydrochloride Drug: Non arotinolol group |
Chronic Kidney Disease | Sumitomo Pharma (Suzhou) Co., Ltd. |
April 2011 | Phase 4 |
| NCT02612298 | Completed | Drug: Arotinolol Hydrochloride Drug: Metoprolol succinate sustained-release tablet |
Essential Hypertension | Sumitomo Pharma (Suzhou) Co., Ltd. |
August 2015 | Phase 4 |
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