Arotinolol
Identification
- Generic Name
- Arotinolol
- DrugBank Accession Number
- DB09204
- Background
Arotinolol is an alpha- and beta-receptor blocker developed in Japan. It is a thiopropanolamine with a tertiary butyl moiety. It has been studied for its potential to be an antihypertensive therapy.6 Artinolol is being developed by Sumitomo Pharmaceutical Co., Ltd. and it is currently under clinical trials.10
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 371.53
Monoisotopic: 371.07959045 - Chemical Formula
- C15H21N3O2S3
- Synonyms
- Arotinolol
- External IDs
- S-596
Pharmacology
- Indication
Artinolol was introduced to be used as an antihypertensive agent since 1986.7 It has been studied for other functions like tremor control for patients with Parkinson disease and it is currently in clinical trials for its use in the control of blood pressure and heart rate.10
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Preclinical studies showed a lack of intrinsic sympathomimetic activities or membrane-establishing properties. It is confirmed that arotinolol presents vasorelaxant activity. This characteristic is also proved to be mainly mediated by its α1-blocking property. In preclinical hypertension trials, there is a specific acute bradycardiac and antihypertensive activity with a pronounced reduction in heart rate. Some reports indicate a delayed development of hypertension when arotinolol is administered daily. Arotinolol has a dose-dependent decrease in cardiac contractility and coronary blood flow as well as an increase in total peripheral resistance. The effects of arotinolol have been confirmed in clinical trials where this drug was able to decrease cardiac index and thus, blood pressure.6
- Mechanism of action
Arotinolol binds to the β1-, β2- and α1- adrenergic receptor sites with a very high affinity. Radioligand studies have shown that arotinolol presents a higher affinity to the β-receptor compared to the α-receptor. The elucidated mechanism of action seems to be the result of a reduction in the cardiac output via the β-blockade and an additional inhibition of the counter-regulatory increase in peripheral resistance mediated by the α-blockade.6
Target Actions Organism ABeta-1 adrenergic receptor antagonistHumans ABeta-2 adrenergic receptor antagonistHumans AAlpha-1 adrenergic receptors antagonistHumans - Absorption
Arotinolol gets rapidly absorbed and distributed in the plasma. The plasma concentration peaks 2 hours after initial administration.5
- Volume of distribution
The stereospecificity of arotinolol is very important for its pharmacokinetic characteristics. The S-enantiomer is highly retained in red blood cells. The distribution studies have shown that arotinolol is mainly distributed from the plasma to the liver followed by the lungs and lastly in the heart. The distribution in the liver was independent on the stereochemistry of the molecules.8
- Protein binding
The stereospecificity of arotinolol is very important for its pharmacokinetic characteristics. Arotinolol is highly bound to serum proteins reaching a ratio of the original dose of 95.3% in the form of the R-enantiomer and 84.5% of the S-enantiomer. The presented stereospecificity is thought to be related to the α1-acid glycoprotein.8
- Metabolism
The stereospecificity of arotinolol is very important for its pharmacokinetic characteristics. The R-enantiomer remains unchanged and it is eliminated from the organism by urine in this form while the S-enantiomer is metabolized.6
- Route of elimination
The stereospecificity of arotinolol is very important for its pharmacokinetic characteristics. Both of the enantiomers were found in urine, suggesting this as the major elimination pathway. It is possible to find arotinolol in urine 2-4 hours after initial administration.6
- Half-life
The reported half-life of arotinolol is 7.2 hours.6
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
The major toxic effects reported for arotinolol-like drugs are the presence of central nervous system depression.9
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Arotinolol which could result in a higher serum level. Abaloparatide The risk or severity of adverse effects can be increased when Abaloparatide is combined with Arotinolol. Abatacept The metabolism of Arotinolol can be increased when combined with Abatacept. Abiraterone The metabolism of Arotinolol can be decreased when combined with Abiraterone. Acarbose The therapeutic efficacy of Acarbose can be increased when used in combination with Arotinolol. - Food Interactions
- Not Available
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- International/Other Brands
- Almarl
Categories
- Drug Categories
- Adrenergic Agents
- Adrenergic Antagonists
- Adrenergic beta-Antagonists
- Agents causing hyperkalemia
- Alcohols
- Amines
- Amino Alcohols
- Bradycardia-Causing Agents
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- Hypotensive Agents
- Neurotransmitter Agents
- Propanols
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as thiophene carboxamides. These are compounds containing a thiophene ring which bears a carboxamide.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Thiophenes
- Sub Class
- Thiophene carboxylic acids and derivatives
- Direct Parent
- Thiophene carboxamides
- Alternative Parents
- 2-heteroaryl carboxamides / Alkylarylthioethers / 2,5-disubstituted thiophenes / 2,4-disubstituted thiazoles / Heteroaromatic compounds / Secondary alcohols / Primary carboxylic acid amides / Amino acids and derivatives / 1,2-aminoalcohols / Sulfenyl compounds show 5 more
- Substituents
- 1,2-aminoalcohol / 2,4-disubstituted 1,3-thiazole / 2,5-disubstituted thiophene / 2-heteroaryl carboxamide / Alcohol / Alkylarylthioether / Amine / Amino acid or derivatives / Aromatic heteromonocyclic compound / Aryl thioether show 21 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 394E3P3B99
- CAS number
- 68377-92-4
- InChI Key
- BHIAIPWSVYSKJS-UHFFFAOYSA-N
- InChI
- 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)
- IUPAC Name
- 5-(2-{[3-(tert-butylamino)-2-hydroxypropyl]sulfanyl}-1,3-thiazol-4-yl)thiophene-2-carboxamide
- SMILES
- CC(C)(C)NCC(O)CSC1=NC(=CS1)C1=CC=C(S1)C(N)=O
References
- General References
- Zhao J, Golozoubova V, Cannon B, Nedergaard J: Arotinolol is a weak partial agonist on beta 3-adrenergic receptors in brown adipocytes. Can J Physiol Pharmacol. 2001 Jul;79(7):585-93. [Article]
- Lee KS, Kim JS, Kim JW, Lee WY, Jeon BS, Kim D: A multicenter randomized crossover multiple-dose comparison study of arotinolol and propranolol in essential tremor. Parkinsonism Relat Disord. 2003 Aug;9(6):341-7. [Article]
- Wu H, Zhang Y, Huang J, Zhang Y, Liu G, Sun N, Yu Z, Zhou Y: Clinical trial of arotinolol in the treatment of hypertension: dippers vs. non-dippers. Hypertens Res. 2001 Sep;24(5):605-10. [Article]
- Miyauchi E, Matsumoto M, Kimura Y, Hattori H, Tsukio Y, Tsuchiya H, Takasaki M, Munehira J, Yamada K, Iwai K, Kawanishi K, Hoshino T, Murai H: [Clinical effect of arotinolol hydrochloride and its influence on renal function in elderly patients with essential hypertension]. Nihon Ronen Igakkai Zasshi. 1999 Aug;36(8):542-6. [Article]
- Nakashima M, Uematsu T, Takiguchi Y, Hashimoto H, Watanabe I, Morioka S, Hibino T: Effect of ophthalmic administration of S-596 (Arotinolol) on intraocular pressure and haemodynamics in health volunteers: comparison with timolol. Eur J Clin Pharmacol. 1985;28(4):391-6. [Article]
- Ganten D. and Mulrow P.J. (1990). Pharmacology of anti-hypertensive therapeutics (1st ed.). Springer .
- Allen R. (1988). Annual reports in medicinal chemistry (23rd ed.). Academic press.
- Kato R., Estabrook W. and Cayen M. (1988). Xenobiotic metabolism and disposition (2nd ed.). Taylor and Francis.
- Pillay V.V. (2013). Modern medical toxicology (4th ed.). Jaypee Brothers.
- Clinical trials [Link]
- External Links
- KEGG Drug
- D07465
- PubChem Compound
- 2239
- PubChem Substance
- 310265112
- ChemSpider
- 2152
- BindingDB
- 81885
- ChEBI
- 135569
- ChEMBL
- CHEMBL93298
- Wikipedia
- Arotinolol
- MSDS
- Download (231 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Treatment Chronic Kidney Disease (CKD) 1 4 Completed Treatment Hypertension, Essential Hypertension 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 149-153ºC 'MSDS' boiling point (°C) 599ºC at 760 mmHg 'MSDS' water solubility Slightly soluble Official Monographs for Pharmacology part I. logP 2.3 'MSDS' - Predicted Properties
Property Value Source Water Solubility 0.0225 mg/mL ALOGPS logP 2.38 ALOGPS logP 2.54 Chemaxon logS -4.2 ALOGPS pKa (Strongest Acidic) 13.51 Chemaxon pKa (Strongest Basic) 9.84 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 88.24 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 96.71 m3·mol-1 Chemaxon Polarizability 40.66 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0ac9-9022000000-cd1515e4fe63b85c28f2 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0ab9-0009000000-1720b492a2f496e48499 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0uki-0009000000-f270bb9bc5c2255fca72 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0bta-3029000000-ccd791d62d54797f77d2 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-001r-0932000000-41a7360022140699fdec Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4i-1691000000-085c06293c2dd7befaea Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4i-6592000000-db368b2ce78e6ba9b3d7 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 173.77574 predictedDeepCCS 1.0 (2019) [M+H]+ 176.13376 predictedDeepCCS 1.0 (2019) [M+Na]+ 182.4246 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Receptor signaling protein activity
- Specific Function
- Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately e...
- Gene Name
- ADRB1
- Uniprot ID
- P08588
- Uniprot Name
- Beta-1 adrenergic receptor
- Molecular Weight
- 51322.1 Da
References
- Ganten D. and Mulrow P.J. (1990). Pharmacology of anti-hypertensive therapeutics (1st ed.). Springer .
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Protein homodimerization activity
- Specific Function
- Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately ...
- Gene Name
- ADRB2
- Uniprot ID
- P07550
- Uniprot Name
- Beta-2 adrenergic receptor
- Molecular Weight
- 46458.32 Da
References
- Ganten D. and Mulrow P.J. (1990). Pharmacology of anti-hypertensive therapeutics (1st ed.). Springer .
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Protein heterodimerization activity
- Specific Function
- This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Components:
Name | UniProt ID |
---|---|
Alpha-1A adrenergic receptor | P35348 |
Alpha-1B adrenergic receptor | P35368 |
Alpha-1D adrenergic receptor | P25100 |
References
- Ganten D. and Mulrow P.J. (1990). Pharmacology of anti-hypertensive therapeutics (1st ed.). Springer .
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Iwaki M, Niwa T, Bandoh S, Itoh M, Hirose H, Kawase A, Komura H: Application of substrate depletion assay to evaluation of CYP isoforms responsible for stereoselective metabolism of carvedilol. Drug Metab Pharmacokinet. 2016 Dec;31(6):425-432. doi: 10.1016/j.dmpk.2016.08.007. Epub 2016 Sep 2. [Article]
- Brodde OE, Kroemer HK: Drug-drug interactions of beta-adrenoceptor blockers. Arzneimittelforschung. 2003;53(12):814-22. [Article]
- Sternieri E, Coccia CP, Pinetti D, Guerzoni S, Ferrari A: Pharmacokinetics and interactions of headache medications, part II: prophylactic treatments. Expert Opin Drug Metab Toxicol. 2006 Dec;2(6):981-1007. doi: 10.1517/17425255.2.6.981 . [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Toxic substance binding
- Specific Function
- Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Serum albumin
- Molecular Weight
- 69365.94 Da
References
- Kato R., Estabrook W. and Cayen M. (1988). Xenobiotic metabolism and disposition (2nd ed.). Taylor and Francis.
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Not Available
- Specific Function
- Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
- Gene Name
- ORM1
- Uniprot ID
- P02763
- Uniprot Name
- Alpha-1-acid glycoprotein 1
- Molecular Weight
- 23511.38 Da
References
- Kato R., Estabrook W. and Cayen M. (1988). Xenobiotic metabolism and disposition (2nd ed.). Taylor and Francis.
Drug created at October 19, 2015 19:52 / Updated at February 21, 2021 18:52