Identification
- Generic Name
- Chlorobutanol
- DrugBank Accession Number
- DB11386
- Background
Chlorobutanol, or chlorbutol, is an alcohol-based preservative with no surfactant activity 5. It also elicits sedative-hypnotic and weak local anesthetic actions in addition to antibacterial and antifungal properties. Similar in nature to chloral hydrate, it is formed by the simple nucleophilic addition of chloroform and acetone.
As a long-term stabilizer of multi-ingredient preparations, chlorobutanol is normally used at a concentration of 0.5%. At this concentration, it also conserves its antimicrobial activity.
Due to the long terminal half-life of 37 days, the use of chlorobutanol as a sedative is limited because of the considerable accumulation which will occur following multiple dosing 3. Chlorobutanol is a common detergent preservative in eye drops and other ophthalmic therapeutic formulations 4.
- Type
- Small Molecule
- Groups
- Approved, Investigational, Vet approved
- Structure
Structure for Chlorobutanol (DB11386)
- Weight
- Average: 177.45
Monoisotopic: 175.9562479 - Chemical Formula
- C4H7Cl3O
- Synonyms
- Chloretone
- Chlorobutanol
Pharmacology
- Indication
No approved therapeutic indications on its own.
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.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to prevent Acute rhinosinusitis Combination Product in combination with: Phenylephrine (DB00388), Chlorpheniramine (DB01114) •••••••••••• •••••••• Used in combination to treat Acute rhinosinusitis Combination Product in combination with: Phenylephrine (DB00388), Chlorpheniramine (DB01114) •••••••••••• •••••••• Used in combination to treat Acute sinusitis Combination Product in combination with: Phenylephrine (DB00388), Chlorpheniramine (DB01114) •••••••••••• •••••••• Management of Infective otitis externa •••••••••••• Used in combination to prevent Pollen allergy Combination Product in combination with: Phenylephrine (DB00388), Chlorpheniramine (DB01114) •••••••••••• •••••••• - Contraindications & Blackbox Warnings
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Chlorobutanol is a detergent preservative with a broad spectrum of antimicrobial activity 4. In vitro, chlorobutanol demonstrated to inhibit platelet aggregation and release via unknown mechanisms 1. A study proposes that the antiplatelet effect of chlorobutanol may occur from inhibition of the arachidonic acid pathway 1. It attenuated thromboxane B2 formation, elevation of cytosolic free calcium, and ATP release, and additionally exhibited a significant inhibitory activity toward several aggregation inducers in a time- and concentration-dependent manner 1. Chlorobutanol may exert a direct negative inotropic effect on myocardial cells to isometric tension produced by the heart 2. Chlorobutanol was shown to induce conjunctival and corneal cell toxicity in vitro: at a concentration of 0.1%, Cbl caused near depletion of the squamous layer while degeneration of corneal epithelial cells, generation of conspicuous membranous blebs, cytoplasmic swelling, and occasional breaks in the external cell membrane were observed at a concentration of 0.5% 4.
- Mechanism of action
As a detergent, chlorobutanol disrupts the lipid structure of the cell membrane and increases the cell permeability, leading to cell lysis 4. It induces conjunctival and corneal cell toxicity via causing cell retraction and cessation of normal cytokines, cell movement, and mitotic activity 4. It disrupts the barrier and transport properties of the corneal epithelium as well as inhibits the utilization of oxygen by the cornea 4. Chlorobutanol also inhibits oxygen use by the cornea, which increases susceptibility to infection 5.
Target Actions Organism UPotassium voltage-gated channel subfamily H member 2 Not Available Humans - Absorption
Following oral administration in healthy subjects, the plasma concentration fell by 50% in 24 hours post-administration 3.
- Volume of distribution
The volume of distribution was approximately 233 ± 141 L in healthy individuals receiving oral chlorobutanol 3.
- Protein binding
The binding to plasma proteins was 57 ± 3% 3.
- Metabolism
Chlorobutanol is reported to undergo glucuronidation and sulphation 3.
- Route of elimination
Under physiological conditions, chlorobutanol is unstable. The mean urinary recovery accounts for 9.6% of the dose orally administered 3.
- Half-life
Following oral administration, the terminal elimination half life in healthy subjects was 10.3 ± 1.3 days 3.
- Clearance
In healthy subjects, the clearance was approximately 11.6 ± 1.0 mL/min following oral administration 3.
- Adverse Effects
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Oral LD50 of anhydrous chlorobutanol in rat is 510 mg/kg MSDS. Chlorobutanol was shown to induce conjunctival and corneal cell toxicity in vitro
- 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.Not Available
- Food Interactions
- No interactions found.
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.- Product Ingredients
Ingredient UNII CAS InChI Key Chlorobutanol hemihydrate 3X4P6271OX 6001-64-5 WRWLCXJYIMRJIN-UHFFFAOYSA-N - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Aurisan Dps Chlorobutanol (15 mg / mL) + Benzocaine (5 mg / mL) + Camphor (30 mg / mL) Solution / drops Auricular (otic) Lab Nadeau LtÉe, Division Of Technilab Inc. 1977-12-31 1999-09-28 Canada 
Balminil Nasal Ointment Chlorobutanol (2 mg / g) + Camphor (4 mg / g) + Ephedrine hydrochloride (6 mg / g) + Eucalyptol (6 mg / g) + Levomenthol (4 mg / g) Ointment Nasal Rougier Pharma Division Of Ratiopharm Inc 1995-12-31 2003-09-22 Canada Cerumol Chlorobutanol (5 %) + Dichlorobenzene (2 %) + Peanut oil (57 %) + Turpentine oil (10 %) Solution / drops Auricular (otic) Thornton & Ross Ltd 1971-12-31 2023-06-09 Canada DİŞİNOL 2 G + 0,5 G + 3,5 G/10 ML ÇÖZELTİ Chlorobutanol (200 mg/10ml) + Clove oil (350 mg/10ml) + Phenol (50 mg/10ml) Solution Oral KOÇAK FARMA İLAÇ VE KİMYA SAN. A.Ş. 2012-01-17 Not applicable Turkey 
Dry Socket Paste Chlorobutanol (1.5 %) + Acetylsalicylic acid (8.33 %) + Eugenol (4.16 %) Paste Dental Sultan Healthcare 1985-12-31 2004-08-06 Canada
Categories
- ATC Codes
- A04AD54 — Chlorobutanol, combinations
- A04AD — Other antiemetics
- A04A — ANTIEMETICS AND ANTINAUSEANTS
- A04 — ANTIEMETICS AND ANTINAUSEANTS
- A — ALIMENTARY TRACT AND METABOLISM
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as tertiary alcohols. These are compounds in which a hydroxy group, -OH, is attached to a saturated carbon atom R3COH (R not H ).
- Kingdom
- Organic compounds
- Super Class
- Organic oxygen compounds
- Class
- Organooxygen compounds
- Sub Class
- Alcohols and polyols
- Direct Parent
- Tertiary alcohols
- Alternative Parents
- Chlorohydrins / Organochlorides / Hydrocarbon derivatives / Alkyl chlorides
- Substituents
- Aliphatic acyclic compound / Alkyl chloride / Alkyl halide / Chlorohydrin / Halohydrin / Hydrocarbon derivative / Organochloride / Organohalogen compound / Tertiary alcohol
- Molecular Framework
- Aliphatic acyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- HM4YQM8WRC
- CAS number
- 57-15-8
- InChI Key
- OSASVXMJTNOKOY-UHFFFAOYSA-N
- InChI
- InChI=1S/C4H7Cl3O/c1-3(2,8)4(5,6)7/h8H,1-2H3
- IUPAC Name
- 1,1,1-trichloro-2-methylpropan-2-ol
- SMILES
- CC(C)(O)C(Cl)(Cl)Cl
References
- General References
- Chen SL, Yang WC, Huang TP, Wann SA, Teng CM: Chlorobutanol, a preservative of desmopressin, inhibits human platelet aggregation and release in vitro. Thromb Haemost. 1990 Nov 30;64(3):473-7. [Article]
- Hermsmeyer K, Aprigliano O: Effects of chlorobutanol and bradykinin on myocardial excitation. Am J Physiol. 1976 Feb;230(2):306-10. doi: 10.1152/ajplegacy.1976.230.2.306. [Article]
- Tung C, Graham GG, Wade DN, Williams KM: The pharmacokinetics of chlorbutol in man. Biopharm Drug Dispos. 1982 Oct-Dec;3(4):371-8. [Article]
- Epstein SP, Ahdoot M, Marcus E, Asbell PA: Comparative toxicity of preservatives on immortalized corneal and conjunctival epithelial cells. J Ocul Pharmacol Ther. 2009 Apr;25(2):113-9. doi: 10.1089/jop.2008.0098. [Article]
- Noecker R: Effects of common ophthalmic preservatives on ocular health. Adv Ther. 2001 Sep-Oct;18(5):205-15. [Article]
- External Links
- KEGG Drug
- D01942
- PubChem Compound
- 5977
- PubChem Substance
- 347827977
- ChemSpider
- 13842993
- BindingDB
- 50417941
- 2378
- ChEBI
- 134813
- ChEMBL
- CHEMBL1439973
- ZINC
- ZINC000001482005
- Wikipedia
- Chlorobutanol
- MSDS
- Download (252 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 Supportive Care Oral Mucositis 1 4 Completed Treatment Ear infection-not otherwise specified / Hearing loss or impairment / Vertigo 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Ointment Nasal Ointment Topical Solution / drops Auricular (otic) Solution Oral Paste Dental Lozenge Oral Liquid Topical Solution Nasal Liquid Dental Liquid Ophthalmic Lotion Ophthalmic - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 99 MSDS boiling point (°C) 167 MSDS - Predicted Properties
Property Value Source Water Solubility 1.65 mg/mL ALOGPS logP 2.31 ALOGPS logP 1.75 Chemaxon logS -2 ALOGPS pKa (Strongest Acidic) 12.59 Chemaxon pKa (Strongest Basic) -3.9 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 1 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 20.23 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 37.27 m3·mol-1 Chemaxon Polarizability 14.75 Å3 Chemaxon Number of Rings 0 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-0900000000-c78e68f4148016414d34 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-00di-0900000000-f1db6c0b14b7dc605505 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4i-0900000000-63de811e85200e97b5bc Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-00di-0900000000-4d9b29de91c6e3b210b0 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-000x-9800000000-a2b448596ef3f88512b6 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-00di-0900000000-0495dea471e57c017345 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]- 110.822308 predictedDarkChem Lite v0.1.0 [M-H]- 127.657776 predictedDeepCCS 1.0 (2019) [M+H]+ 111.664208 predictedDarkChem Lite v0.1.0 [M+H]+ 130.63275 predictedDeepCCS 1.0 (2019) [M+Na]+ 110.925508 predictedDarkChem Lite v0.1.0 [M+Na]+ 139.54196 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
- Specific Function
- Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...
- Gene Name
- KCNH2
- Uniprot ID
- Q12809
- Uniprot Name
- Potassium voltage-gated channel subfamily H member 2
- Molecular Weight
- 126653.52 Da
References
- Friemel A, Zunkler BJ: Interactions at human ether-a-go-go-related gene channels. Toxicol Sci. 2010 Apr;114(2):346-55. doi: 10.1093/toxsci/kfq011. Epub 2010 Jan 13. [Article]
Drug created at February 25, 2016 18:19 / Updated at October 20, 2021 17:29