Chlorobutanol

Identification

Name
Chlorobutanol
Accession Number
DB11386
Type
Small Molecule
Groups
Approved, Investigational, Vet approved
Description

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.

Structure
Thumb
Synonyms
  • Chloretone
  • Chlorobutanol
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Aurisan DpsChlorobutanol (15 mg) + Benzocaine (5 mg) + Camphor (30 mg)Solution / dropsAuricular (otic)Lab Nadeau LtÉe, Division Of Technilab Inc.1977-12-311999-09-28Canada
Balminil Nasal OintmentChlorobutanol (2 mg) + Camphor (4 mg) + Ephedrine hydrochloride (6 mg) + Eucalyptol (6 mg) + Levomenthol (4 mg)OintmentNasalRougier Pharma Division Of Ratiopharm Inc1995-12-312003-09-22Canada
CerumolChlorobutanol (5 %) + Dichlorobenzene (2 %) + Peanut oil (57 %) + Turpentine oil (10 %)Solution / dropsAuricular (otic)Thornton & Ross Ltd1971-12-31Not applicableCanada
Dry Socket PasteChlorobutanol (1.5 %) + Acetylsalicylic acid (8.33 %) + Eugenol (4.16 %)PasteDentalSultan Healthcare1985-12-312004-08-06Canada
Gouttes Pour Mal D'oreillesChlorobutanol (1.63 g) + Benzocaine (550 mg) + Camphor (3.43 g)Solution / dropsAuricular (otic)Lab Valmo EnregistrÉ, Division Of Technilab Inc.1983-12-312000-08-24Canada
Larynsol LozChlorobutanol (.6 mg) + Benzoic acid (5 mg) + Eucalyptol (3.2 mg)LozengeOralHerbes Universelles Inc.1979-12-312009-07-15Canada
Neutralite LiqChlorobutanol (1.41875 kg) + Monopotassium phosphate (34.3905 kg) + Sodium phosphate, dibasic (35.69575 kg)LiquidTopicalCanadian Custom Packaging Company1964-12-312012-11-20Canada
Oralgar DpsChlorobutanol (490 mg) + Benzocaine (165 mg) + Camphor (1.03 g)Solution / dropsAuricular (otic)Produits Marc O (1987) Inc., Division Of Technilab Inc.1989-12-151999-09-17Canada
Outgro LiquidChlorobutanol (4.7 %) + Tannic acid (23.5 %)LiquidTopicalWhitehall Robins Inc.1993-12-311997-08-07Canada
Rhino-vaccinChlorobutanol (2 mg) + Camphor (4 mg) + Ephedrine hydrochloride (6 mg) + Eucalyptol (6 mg) + Levomenthol (4 mg)OintmentNasalRougier Pharma Division Of Ratiopharm Inc1951-12-312009-08-04Canada
Categories
UNII
HM4YQM8WRC
CAS number
57-15-8
Weight
Average: 177.45
Monoisotopic: 175.9562479
Chemical Formula
C4H7Cl3O
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

Pharmacology

Indication

No approved therapeutic indications on its own.

Associated Conditions
Pharmacodynamics

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.

TargetActionsOrganism
UPotassium voltage-gated channel subfamily H member 2Not AvailableHumans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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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.

Toxicity

Oral LD50 of anhydrous chlorobutanol in rat is 510 mg/kg MSDS. Chlorobutanol was shown to induce conjunctival and corneal cell toxicity in vitro

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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.

References

General References
  1. 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. [PubMed:2096493]
  2. 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. [PubMed:1083146]
  3. Tung C, Graham GG, Wade DN, Williams KM: The pharmacokinetics of chlorbutol in man. Biopharm Drug Dispos. 1982 Oct-Dec;3(4):371-8. [PubMed:7159691]
  4. 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. [PubMed:19284328]
  5. Noecker R: Effects of common ophthalmic preservatives on ocular health. Adv Ther. 2001 Sep-Oct;18(5):205-15. [PubMed:11783457]
External Links
KEGG Drug
D01942
PubChem Compound
5977
PubChem Substance
347827977
ChemSpider
13842993
BindingDB
50417941
RxNav
2378
ChEBI
134813
ChEMBL
CHEMBL1439973
ZINC
ZINC000001482005
Wikipedia
Chlorobutanol
ATC Codes
A04AD54 — Chlorobutanol, combinationsA04AD04 — Chlorobutanol
MSDS
Download (252 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedSupportive CareOral Mucositis1
4CompletedTreatmentEar infection-not otherwise specified / Hearing loss or impairment / Vertigo1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
OintmentNasal
Solution / dropsAuricular (otic)
PasteDental
LozengeOral
LiquidTopical
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)99MSDS
boiling point (°C)167MSDS
Predicted Properties
PropertyValueSource
Water Solubility1.65 mg/mLALOGPS
logP2.31ALOGPS
logP1.75ChemAxon
logS-2ALOGPS
pKa (Strongest Acidic)12.59ChemAxon
pKa (Strongest Basic)-3.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area20.23 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity37.27 m3·mol-1ChemAxon
Polarizability14.75 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Tertiary alcohol / Halohydrin / Chlorohydrin / Hydrocarbon derivative / Organochloride / Organohalogen compound / Alkyl halide / Alkyl chloride / Aliphatic acyclic compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
Not Available

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
  1. 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. [PubMed:20071423]

Drug created on February 25, 2016 11:19 / Updated on May 10, 2020 23:53

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