Identification
- Summary
Butamben is anesthesia of mucus membranes other than the eyes.
- Brand Names
- Cetacaine, One Touch Reformulated Apr 2009
- Generic Name
- Butamben
- DrugBank Accession Number
- DB11148
- Background
Butamben is a local anesthetic in the form of n-butyl-p-aminobenzoate.1 Its structure corresponds to the standard molecule of a hydrophilic and hydrophobic domain separated by an intermediate ester found in most of the local anesthetics. Due to its very low water solubility, butamben is considered to be suitable only for topical anesthesia. The FDA removed all parenteral butamben products from the market, possibly due to the poor solubility of this drug.5,12
- Type
- Small Molecule
- Groups
- Approved, Withdrawn
- Structure
Structure for Butamben (DB11148)
- Weight
- Average: 193.246
Monoisotopic: 193.110278727 - Chemical Formula
- C11H15NO2
- Synonyms
- Butamben
- Butyl aminobenzoate
- External IDs
- NSC-128464
Pharmacology
- Indication
Butamben was indicated for the treatment of chronic pain due to its long-duration effect.3 It is also indicated as a surface anesthetic for skin a mucous membrane and for the relief of pain and pruritus associated with anorectal disorders.11
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Butamben has been shown to selectively inhibit dorsal root pain signal transmission for periods of months when administered as epidural suspensions.1 The effect of butamben is not related to any significant loss of motor function which indicates that it targets specifically the pain-sensing C fibers of the dorsal root.3 When administered topically, butamben produced anesthesia by accumulating in the nerve cell membrane causing it to expand and lose its ability to depolarize and blocking the impulse transmission.6
- Mechanism of action
Butamben acts by inhibiting the voltage-gated calcium channels in dorsal root ganglion neurons.2 The modification in this channels is thought to cause a disturbance of the channel kinetics acceleration.1 It is reported as well that butamben is an inhibitor of the sodium channels and a delayed rectifier of potassium currents. All the effects of butamben are performed in the root ganglion neurons which suggests that the related anesthetic effect may be caused by the reduced electrical excitability.3
Target Actions Organism AVoltage-dependent calcium channel inhibitorHumans AATP-sensitive potassium channel antagonistHumans UTransient receptor potential cation channel subfamily A member 1 inhibitorHumans UTransient receptor potential cation channel subfamily V member 4 inhibitorHumans - Absorption
When butamben is administered epidurally in a suspension form, the physical characteristics of butamben allow a very slow release.11 When administered topically, butamben is also reported to have a very low systemic absorption which allows for a longer duration of action.7
- Volume of distribution
This pharmacokinetic property has not been determined.
- Protein binding
As all other local anesthetics, it is thought that butamben will be highly bound to plasma proteins, mainly to alpha-1-acid glycoprotein.4
- Metabolism
The metabolic pathway of butamben follows the same pattern of other local anesthetics and it is driven mainly by the hydrolysis via cholinesterase for the formation of inert metabolites.8
- Route of elimination
The metabolites found in plasma after cholinesterase processing are disposed of in the urine.8
- Half-life
The effective half-life of unencapsulated butamben is registered to be of 90 minutes. Some efforts were made to prepare D, L-lactic acid capsules which increased the half-life of butamben to even 400 hours.10
- Clearance
Clearance is flow-limited and it highly depends on the state of protein-bound form.4
- Adverse Effects
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In studies, the most common effect was related to the generation of a prolonged effect. It was also shown in preclinical trials to produce tissue necrosis and neuritis. The LD50 of butamben is registered to be of 67 mg/kg.9
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbemaciclib The risk or severity of methemoglobinemia can be increased when Abemaciclib is combined with Butamben. Abiraterone The risk or severity of methemoglobinemia can be increased when Abiraterone is combined with Butamben. Acetaminophen The risk or severity of methemoglobinemia can be increased when Acetaminophen is combined with Butamben. Acetazolamide The risk or severity of methemoglobinemia can be increased when Acetazolamide is combined with Butamben. Acetic acid The risk or severity of methemoglobinemia can be increased when Acetic acid is combined with Butamben. - 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 Butamben picrate D4ZFB7ZH5Y 577-48-0 ATAGSVCDFKGYPE-UHFFFAOYSA-N - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Cetacaine Liquid Butamben (2 %) + Benzocaine (14 %) + Tetracaine hydrochloride (2 %) Liquid Topical Cetylite Industries, Inc. 1996-09-19 Not applicable Canada 
Cetacaine Spray Butamben (2 %) + Benzocaine (14 %) + Tetracaine hydrochloride (2 %) Aerosol Topical Cetylite Industries, Inc. 1994-12-31 Not applicable Canada - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Cetacaine Anesthetic Butamben (0.004 g/0.2g) + Benzocaine (0.028 g/0.2g) + Tetracaine hydrochloride (0.004 g/0.2g) Solution Topical Cetylite Industries, Inc. 1960-01-01 Not applicable US 
Cetacaine Anesthetic Butamben (0.004 g/0.2g) + Benzocaine (0.028 g/0.2g) + Tetracaine hydrochloride (0.004 g/0.2g) Aerosol, spray Topical Cetylite Industries, Inc. 1958-01-01 Not applicable US Cetacaine Anesthetic Butamben (0.004 g/0.2g) + Benzocaine (0.028 g/0.2g) + Tetracaine hydrochloride (0.004 g/0.2g) Solution Topical Cetylite Industries, Inc. 1960-01-01 Not applicable US Cetacaine Anesthetic Butamben (0.004 g/0.2g) + Benzocaine (0.028 g/0.2g) + Tetracaine hydrochloride (0.004 g/0.2g) Solution Topical Cetylite Industries, Inc. 1960-01-01 Not applicable US Cetacaine Topical Anesthetic Butamben (0.004 g/0.2g) + Benzocaine (0.028 g/0.2g) + Tetracaine hydrochloride (0.004 g/0.2g) Gel Topical Cetylite Industries, Inc. 1960-01-01 Not applicable US
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as benzoic acid esters. These are ester derivatives of benzoic acid.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Benzoic acids and derivatives
- Direct Parent
- Benzoic acid esters
- Alternative Parents
- Aminobenzoic acids and derivatives / Benzoyl derivatives / Aniline and substituted anilines / Carboxylic acid esters / Amino acids and derivatives / Monocarboxylic acids and derivatives / Primary amines / Organopnictogen compounds / Organooxygen compounds / Organic oxides show 1 more
- Substituents
- Amine / Amino acid or derivatives / Aminobenzoic acid or derivatives / Aniline or substituted anilines / Aromatic homomonocyclic compound / Benzoate ester / Benzoyl / Carboxylic acid derivative / Carboxylic acid ester / Hydrocarbon derivative show 8 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- substituted aniline, primary amino compound, benzoate ester, amino acid ester (CHEBI:3231)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- EFW857872Q
- CAS number
- 94-25-7
- InChI Key
- IUWVALYLNVXWKX-UHFFFAOYSA-N
- InChI
- InChI=1S/C11H15NO2/c1-2-3-8-14-11(13)9-4-6-10(12)7-5-9/h4-7H,2-3,8,12H2,1H3
- IUPAC Name
- butyl 4-aminobenzoate
- SMILES
- CCCCOC(=O)C1=CC=C(N)C=C1
References
- General References
- Beekwilder JP, van Kempen GT, van den Berg RJ, Ypey DL: The local anesthetic butamben inhibits and accelerates low-voltage activated T-type currents in small sensory neurons. Anesth Analg. 2006 Jan;102(1):141-5. [Article]
- Beekwilder JP, Winkelman DL, van Kempen GT, van den Berg RJ, Ypey DL: The block of total and N-type calcium conductance in mouse sensory neurons by the local anesthetic n-butyl-p-aminobenzoate. Anesth Analg. 2005 Jun;100(6):1674-9. doi: 10.1213/01.ANE.0000151162.07211.DD. [Article]
- Winkelman DL, Beck CL, Ypey DL, O'Leary ME: Inhibition of the A-type K+ channels of dorsal root ganglion neurons by the long-duration anesthetic butamben. J Pharmacol Exp Ther. 2005 Sep;314(3):1177-86. doi: 10.1124/jpet.105.087759. Epub 2005 May 27. [Article]
- Shipton EA: New formulations of local anaesthetics-part I. Anesthesiol Res Pract. 2012;2012:546409. doi: 10.1155/2012/546409. Epub 2011 Dec 5. [Article]
- Mura P, Maestrelli F, Cirri M, Nerli G, Di Cesare Mannelli L, Ghelardini C, Mennini N: Improvement of Butamben Anesthetic Efficacy by the Development of Deformable Liposomes Bearing the Drug as Cyclodextrin Complex. Pharmaceutics. 2021 Jun 12;13(6). pii: pharmaceutics13060872. doi: 10.3390/pharmaceutics13060872. [Article]
- Schilling J. (2004). Pharmacology. A2-in-1 reference for nurses. Lippincott Williams & Wilkins. [ISBN:1-58255-320-3]
- Buch J. (2010). Clinically oriented pharmacology (2nd ed.). PDU Medical College.
- Daskalos D. (2012). Local anesthesia for the dental hygienist. Elsevier. [ISBN:978-0323-07371-4]
- Rossoff I. (1974). Handbook of veterinary drugs. Springer.
- Whateley T. (1992). Microencapsulation of drugs. Hardwood Academic Publishers.. [ISBN:3-7186-5247-1]
- Tesis [Link]
- Code of Federal Regulations 216.24: Drug products withdrawn or removed from the market for reasons of safety or effectiveness. [Link]
- External Links
- Human Metabolome Database
- HMDB0249473
- KEGG Compound
- C07875
- PubChem Compound
- 2482
- PubChem Substance
- 347827919
- ChemSpider
- 2388
- BindingDB
- 50240094
- 19861
- ChEBI
- 3231
- ChEMBL
- CHEMBL127516
- ZINC
- ZINC000001530937
- Wikipedia
- Butamben
- MSDS
- Download (48.1 KB)
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Solution Topical Liquid Topical Aerosol Topical Gel Topical Aerosol, spray Topical Gel Dental; Topical - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 58 ºC 'MSDS' boiling point (°C) 173.5 ºC 'MSDS' water solubility 140 mg/L Petrus J. Thesis. 1973. logP 2.87 'MSDS' pKa 2.472 Toxnet - Predicted Properties
Property Value Source Water Solubility 0.336 mg/mL ALOGPS logP 2.88 ALOGPS logP 2.47 Chemaxon logS -2.8 ALOGPS pKa (Strongest Basic) 2.76 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 52.32 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 56.66 m3·mol-1 Chemaxon Polarizability 21.96 Å3 Chemaxon Number of Rings 1 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
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 149.507874 predictedDarkChem Lite v0.1.0 [M-H]- 148.327174 predictedDarkChem Lite v0.1.0 [M-H]- 146.5675 predictedDeepCCS 1.0 (2019) [M+H]+ 150.780874 predictedDarkChem Lite v0.1.0 [M+H]+ 148.773974 predictedDarkChem Lite v0.1.0 [M+H]+ 150.02727 predictedDeepCCS 1.0 (2019) [M+Na]+ 150.291874 predictedDarkChem Lite v0.1.0 [M+Na]+ 158.9659 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Voltage-gated calcium channel activity
- Specific Function
- This protein is a subunit of the dihydropyridine (DHP) sensitive calcium channel. Plays a role in excitation-contraction coupling. The skeletal muscle DHP-sensitive Ca(2+) channel may function only...
Components:
References
- Beekwilder JP, Winkelman DL, van Kempen GT, van den Berg RJ, Ypey DL: The block of total and N-type calcium conductance in mouse sensory neurons by the local anesthetic n-butyl-p-aminobenzoate. Anesth Analg. 2005 Jun;100(6):1674-9. doi: 10.1213/01.ANE.0000151162.07211.DD. [Article]
- Beekwilder JP, van Kempen GT, van den Berg RJ, Ypey DL: The local anesthetic butamben inhibits and accelerates low-voltage activated T-type currents in small sensory neurons. Anesth Analg. 2006 Jan;102(1):141-5. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Phosphatidylinositol-4,5-bisphosphate binding
- Specific Function
- In the kidney, probably plays a major role in potassium homeostasis. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than...
Components:
References
- Winkelman DL, Beck CL, Ypey DL, O'Leary ME: Inhibition of the A-type K+ channels of dorsal root ganglion neurons by the long-duration anesthetic butamben. J Pharmacol Exp Ther. 2005 Sep;314(3):1177-86. doi: 10.1124/jpet.105.087759. Epub 2005 May 27. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Temperature-gated cation channel activity
- Specific Function
- Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function (PubMed:25389312, PubMed:25855297). Has a central role in t...
- Gene Name
- TRPA1
- Uniprot ID
- O75762
- Uniprot Name
- Transient receptor potential cation channel subfamily A member 1
- Molecular Weight
- 127499.88 Da
References
- Bang S, Yang TJ, Yoo S, Heo TH, Hwang SW: Inhibition of sensory neuronal TRPs contributes to anti-nociception by butamben. Neurosci Lett. 2012 Jan 11;506(2):297-302. doi: 10.1016/j.neulet.2011.11.026. Epub 2011 Nov 23. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity. Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification (PubMed:18826956, PubMed:18695040). Also activated by heat, low pH, citrate and phorbol esters (PubMed:18826956, PubMed:18695040). Increase of intracellular Ca(2+) potentiates currents. Channel activity seems to be regulated by a calmodulin-dependent mechanism with a negative feedback mechanism (PubMed:12724311, PubMed:18826956). Promotes cell-cell junction formation in skin keratinocytes and plays an important role in the formation and/or maintenance of functional intercellular barriers (By similarity). Acts as a regulator of intracellular Ca(2+) in synoviocytes (PubMed:19759329). Plays an obligatory role as a molecular component in the nonselective cation channel activation induced by 4-alpha-phorbol 12,13-didecanoate and hypotonic stimulation in synoviocytes and also regulates production of IL-8 (PubMed:19759329). Together with PKD2, forms mechano- and thermosensitive channels in cilium (PubMed:18695040). Negatively regulates expression of PPARGC1A, UCP1, oxidative metabolism and respiration in adipocytes (By similarity). Regulates expression of chemokines and cytokines related to proinflammatory pathway in adipocytes (By similarity). Together with AQP5, controls regulatory volume decrease in salivary epithelial cells (By similarity). Required for normal development and maintenance of bone and cartilage (PubMed:26249260).
- Specific Function
- Actin binding
- Gene Name
- TRPV4
- Uniprot ID
- Q9HBA0
- Uniprot Name
- Transient receptor potential cation channel subfamily V member 4
- Molecular Weight
- 98280.2 Da
References
- Bang S, Yang TJ, Yoo S, Heo TH, Hwang SW: Inhibition of sensory neuronal TRPs contributes to anti-nociception by butamben. Neurosci Lett. 2012 Jan 11;506(2):297-302. doi: 10.1016/j.neulet.2011.11.026. Epub 2011 Nov 23. [Article]
- Winkelman DL, Beck CL, Ypey DL, O'Leary ME: Inhibition of the A-type K+ channels of dorsal root ganglion neurons by the long-duration anesthetic butamben. J Pharmacol Exp Ther. 2005 Sep;314(3):1177-86. doi: 10.1124/jpet.105.087759. Epub 2005 May 27. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Identical protein binding
- Specific Function
- Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
- Gene Name
- BCHE
- Uniprot ID
- P06276
- Uniprot Name
- Cholinesterase
- Molecular Weight
- 68417.575 Da
References
- Daskalos D. (2012). Local anesthesia for the dental hygienist. Elsevier. [ISBN:978-0323-07371-4]
Carriers
- 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
- Shipton EA: New formulations of local anaesthetics-part I. Anesthesiol Res Pract. 2012;2012:546409. doi: 10.1155/2012/546409. Epub 2011 Dec 5. [Article]
- 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
- Shipton EA: New formulations of local anaesthetics-part I. Anesthesiol Res Pract. 2012;2012:546409. doi: 10.1155/2012/546409. Epub 2011 Dec 5. [Article]
Drug created at December 03, 2015 16:51 / Updated at November 11, 2022 16:49