Identification

Name
Benzonatate
Accession Number
DB00868  (APRD00629)
Type
Small Molecule
Groups
Approved
Description

Benzonatate is a non-narcotic oral antitussive (cough suppressant) drug which works by anesthetizing the tissues of the lungs and pleura responsible for the cough reflex. It is chemically related to other ester anesthetics such as procaine. It has an anesthetic (numbing) action similar to that of benzocaine and "numbs" the stretch sensors in the lungs. It is the stretching of these sensors with breathing that causes the cough. It was approved by the FDA in 1958.

Structure
Thumb
Synonyms
  • 2-[2-[2-[2-[2-[2-[2-[2-(2-Methoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl 4-butylaminobenzoate
  • 2,5,8,11,14,17,20,23,26-Nonaoxaoctacosan-28-yl P-(butylamino)benzoate
  • 3,6,9,12,15,18,21,24,27-Nonaoxaoctacosyl 4-butylaminobenzoate
  • 4-(Butylamino)benzoic acid 3,6,9,12,15,18,21,24,27-nonaoxaoctacos-1-yl ester
  • Benzonatat
  • Benzonatate
  • Benzonatato
  • Benzonatatum
  • Benzononatine
  • Nonaethyleneglycol monomethyl ether P-N-butylaminobenzoate
  • P-Butylaminobenzoic acid omega-O-methylnonaethyleneglycol ester
External IDs
KM 65
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TessalonCapsule100 mg/1OralPfizer Laboratories Div Pfizer Inc.1958-02-10Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BenzonatateCapsule200 mg/1OralPreferreed Pharmaceuticals Inc.2017-08-29Not applicableUs
BenzonatateCapsule200 mg/1OralZydus Pharmaceuticals Usa, Inc.2007-04-09Not applicableUs
BenzonatateCapsule150 mg/1OralAscend Laboratories, LLC2015-02-09Not applicableUs
BenzonatateCapsule, liquid filled100 mg/1OralA S Medication Solutions2010-06-04Not applicableUs
BenzonatateCapsule200 mg/1OralLake Erie Medical Dba Quality Care Produts Llc2015-06-01Not applicableUs
BenzonatateCapsule200 mg/1OralGolden State Medical Supply2007-07-252018-02-28Us
BenzonatateCapsule150 mg/1OralAscend Laboratories, LLC2017-03-22Not applicableUs
BenzonatateCapsule, liquid filled200 mg/1Oralbryant ranch prepack2010-06-04Not applicableUs
BenzonatateCapsule100 mg/1OralNu Care Pharmaceuticals,inc.2007-04-09Not applicableUs
BenzonatateCapsule100 mg/1OralKaiser Foundations Hospitals2010-06-21Not applicableUs
International/Other Brands
Tesaperl (Novartis )
Categories
UNII
5P4DHS6ENR
CAS number
104-31-4
Weight
Average: 603.7419
Monoisotopic: 603.361861543
Chemical Formula
C30H53NO11
InChI Key
MAFMQEKGGFWBAB-UHFFFAOYSA-N
InChI
InChI=1S/C30H53NO11/c1-3-4-9-31-29-7-5-28(6-8-29)30(32)42-27-26-41-25-24-40-23-22-39-21-20-38-19-18-37-17-16-36-15-14-35-13-12-34-11-10-33-2/h5-8,31H,3-4,9-27H2,1-2H3
IUPAC Name
2,5,8,11,14,17,20,23,26-nonaoxaoctacosan-28-yl 4-(butylamino)benzoate
SMILES
CCCCNC1=CC=C(C=C1)C(=O)OCCOCCOCCOCCOCCOCCOCCOCCOCCOC

Pharmacology

Indication

For the symptomatic relief of cough. Has also been applied locally in the oral cavity in adults by releasing the drug from the liquid-filled capsules to provide oropharyngeal anesthesia for conscious intubation.

Structured Indications
Pharmacodynamics

Benzonatate, a non-narcotic antitussive agent chemically related to tetracaine and other ester-type local anesthetics, is used to suppress cough associated with both acute and chronic respiratory conditions. The drug acts peripherally by anesthetizing the stretch receptors located in the respiratory passages, lungs, and pleura through the dampening of their activity, which reduces the cough reflex.

Mechanism of action

Benzonatate acts peripherally, anesthetizing the stretch receptors of vagal afferent fibers in the alveoli of the lungs, bronchi, and pleura. Since these receptors are responsible for mediating the cough reflex, anesthetizing these receptors result in the inhibiton of cough production. Benzonatate also suppresses transmission of the cough reflex at the level of the medulla where the afferent impulse is transmitted to the motor nerves. When applied locally, Benzonatate binds within the intracellular portion of voltage-gated sodium channels, decreasing the rate of membrane depolarization and increasing the threshold for electrical excitability.

TargetActionsOrganism
USodium channel protein type 5 subunit alpha
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Benzonatate is hydrolyzed to para-aminobenzoic acid (PABA) by plasma esterases

Route of elimination
Not Available
Half life

3-8 hours

Clearance
Not Available
Toxicity

Restlessness, tremors, seizures and unconsciousness.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
No interactions found.
Food Interactions
  • Take without regard to meals.

References

Synthesis Reference

Matter, M.; U.S. Patent 2,714,608; August 2, 1955; assigned to Ciba Pharmaceutical Products, Inc.

General References
  1. Cohen V, Jellinek SP, Stansfield L, Truong H, Baseluos C, Marshall JP: Cardiac arrest with residual blindness after overdose of Tessalon(R) (benzonatate) perles. J Emerg Med. 2011 Aug;41(2):166-71. doi: 10.1016/j.jemermed.2009.08.027. Epub 2009 Nov 5. [PubMed:19892505]
External Links
Human Metabolome Database
HMDB15006
KEGG Drug
D00242
PubChem Compound
7699
PubChem Substance
46506376
ChemSpider
7413
ChEBI
3032
ChEMBL
CHEMBL1374379
Therapeutic Targets Database
DAP000514
PharmGKB
PA164745459
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Benzonatate
ATC Codes
R05DB01 — Benzonatate

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceHealthy Volunteers1

Pharmacoeconomics

Manufacturers
  • Banner pharmacaps inc
  • Kv pharmaceutical co
  • Mikart inc
  • Orit laboratories llc
  • Sun pharmaceutical industries inc
  • The pharma network llc
  • Zydus pharmaceuticals usa inc
  • Forest laboratories inc
Packagers
Dosage forms
FormRouteStrength
CapsuleOral100 mg/1
CapsuleOral150 mg/1
CapsuleOral200 mg/1
Capsule, gelatin coatedOral200 mg/1
Capsule, liquid filledOral100 mg/1
Capsule, liquid filledOral200 mg/1
TabletOral100 mg/1
Prices
Unit descriptionCostUnit
Tessalon 200 mg capsule2.76USD capsule
Benzonatate 200 mg capsule2.03USD capsule
Tessalon Perles 100 mg capsule1.62USD capsule
Zonatuss 150 mg capsule1.59USD capsule
Tessalon perle 100 mg capsule1.4USD capsule
Benzonatate 100 mg capsule0.85USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
water solubilitySoluble in most organic solvents except aliphatic hydrocarbonsNot Available
logP2.45HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.00159 mg/mLALOGPS
logP2.09ALOGPS
logP2.35ChemAxon
logS-5.6ALOGPS
pKa (Strongest Basic)3.47ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count11ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area121.4 Å2ChemAxon
Rotatable Bond Count33ChemAxon
Refractivity161.54 m3·mol-1ChemAxon
Polarizability67.87 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9932
Blood Brain Barrier+0.9355
Caco-2 permeable+0.6067
P-glycoprotein substrateSubstrate0.6531
P-glycoprotein inhibitor INon-inhibitor0.5978
P-glycoprotein inhibitor IINon-inhibitor0.9434
Renal organic cation transporterNon-inhibitor0.7646
CYP450 2C9 substrateNon-substrate0.875
CYP450 2D6 substrateNon-substrate0.7017
CYP450 3A4 substrateNon-substrate0.6026
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9232
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9275
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.932
Ames testNon AMES toxic0.7269
CarcinogenicityNon-carcinogens0.9182
BiodegradationReady biodegradable0.6331
Rat acute toxicity2.2423 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9013
hERG inhibition (predictor II)Non-inhibitor0.6129
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-2900000000-3718c62c83080a92ccdd

Taxonomy

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 / Phenylalkylamines / Benzoyl derivatives / Aniline and substituted anilines / Secondary alkylarylamines / Carboxylic acid esters / Amino acids and derivatives / Monocarboxylic acids and derivatives / Dialkyl ethers / Organopnictogen compounds
show 2 more
Substituents
Aminobenzoic acid or derivatives / Benzoate ester / Benzoyl / Aniline or substituted anilines / Phenylalkylamine / Secondary aliphatic/aromatic amine / Amino acid or derivatives / Carboxylic acid ester / Carboxylic acid derivative / Secondary amine
show 12 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
substituted aniline, secondary amino compound, benzoate ester (CHEBI:3032)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Voltage-gated sodium channel activity involved in sa node cell action potential
Specific Function
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the pr...
Gene Name
SCN5A
Uniprot ID
Q14524
Uniprot Name
Sodium channel protein type 5 subunit alpha
Molecular Weight
226937.475 Da
References
  1. Thimann DA, Huang CJ, Goto CS, Feng SY: Benzonatate toxicity in a teenager resulting in coma, seizures, and severe metabolic acidosis. J Pediatr Pharmacol Ther. 2012 Jul;17(3):270-3. doi: 10.5863/1551-6776-17.3.270. [PubMed:23258970]

Drug created on June 13, 2005 07:24 / Updated on October 02, 2017 04:47