Accession Number
DB00868  (APRD00629)
Small Molecule

Benzonatate is an oral antitussive drug used in the relief and suppression of cough in patients older than ten years of age.3 Currently, benzonatate is the only non-narcotic antitussive available as a prescription drug.2 It works to reduce the activity of cough reflex by desensitizing the tissues of the lungs and pleura involved in the cough reflex. Benzonatate was approved by the FDA in 1958 under the market name Tessalon Perles.3 Because its chemical structure resembles that of the anesthetic agents in the para-amino-benzoic acid class (such as procaine and tetracaine), benzonatate exhibits anesthetic or numbing action.7 Although it not prone to drug misuse or abuse, benzonatate is associated with a risk for severe toxicity and overdose, especially in children.4

  • 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 ω-O-methylnonaethyleneglycol ester
External IDs
KM 65 / KM65
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BenzonatateCapsule100 mg/1OralGreenstone LLC2020-01-06Not applicableUs
BenzonatateCapsule200 mg/1OralEthex Corporation2008-12-30Not applicableUs
BenzonatateCapsule100 mg/1OralEthex Corporation2008-12-30Not applicableUs
TessalonCapsule100 mg/1OralPfizer Laboratories Div Pfizer Inc1958-02-10Not applicableUs
TessalonCapsule200 mg/1OralPfizer Laboratories1999-06-252011-02-04Us
TessalonCapsule100 mg/1OralPhysicians Total Care, Inc.1958-02-102011-07-31Us
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BenzonatateCapsule, liquid filled200 mg/1OralREMEDYREPACK INC.2017-11-10Not applicableUs
BenzonatateCapsule100 mg/1OralUnit Dose Services2007-07-25Not applicableUs
BenzonatateCapsule200 mg/1Oralbryant ranch prepack2015-08-10Not applicableUs
BenzonatateCapsule200 mg/1OralAscend Laboratories LLC2017-03-22Not applicableUs
BenzonatateCapsule100 mg/1OralRemedy Repack2013-04-022016-05-06Us
BenzonatateCapsule, liquid filled100 mg/1OralREMEDYREPACK INC.2016-11-18Not applicableUs
BenzonatateCapsule100 mg/1OralAidarex Pharmaceuticals LLC2007-07-25Not applicableUs
BenzonatateCapsule200 mg/1OralNucare Pharmaceuticals,inc.2018-12-21Not applicableUs
BenzonatateCapsule100 mg/1OralXLCare Pharmaceuticals, Inc2020-02-17Not applicableUs
BenzonatateCapsule100 mg/1OralH.J. Harkins Company2007-07-25Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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International/Other Brands
Exangit / Tesaperl (Novartis ) / Tessalon Perles / Ventussin
CAS number
Average: 603.7419
Monoisotopic: 603.361861543
Chemical Formula
InChI Key
2,5,8,11,14,17,20,23,26-nonaoxaoctacosan-28-yl 4-(butylamino)benzoate



Benzonatate is indicated for the symptomatic relief of cough.7

Associated Conditions

Benzonatate suppresses cough associated with both acute and chronic respiratory conditions. Its works by desensitizing the pulmonary stretch receptors involved in the cough reflex. There are limited clinical trials of benzonatate; however, earlier studies demonstrated inhibition of experimentally-induced cough and subjectively-measured pathological cough by benzonatate.1

Benzonatate has no inhibitory effects on the respiratory center in recommended dosage. Its onset of action is within 15 to 20 minutes following administration and its duration of effect is about 3 to 8 hours.7

Mechanism of action

Benzonatate is a local anesthetic drug that acts peripherally by anesthetizing and reducing the activity of vagal stretch receptors or nerve fibres located in the respiratory passages, lungs, and pleura.2,7 Once the stretch receptors are stimulated, they send impulses to the cough centre located in the medulla via an afferent pathway consisting of sensory nerve fibres or the vagus nerve. The efferent signal is then generated that sends impulses to the expiratory muscles to produce a cough.6 Anesthetizing these receptors by benzonatate results in the inhibition of the cough reflex activity and cough production.2,7 Benzonatate also inhibits the transmission of impulses of the cough reflex in the vagal nuclei of the medulla.5 There are several proposed mechanisms of benzonatate; it is also a potent voltage-gated sodium channel inhibitor.2

USodium channel protein type 5 subunit alpha
Additional Data Available
Adverse Effects

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Blackbox Warnings

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Following oral administration, benzonatate enters the systemic circulation via gastrointestinal absorption.3 The Cmax of benzonatate following oral administration of 100 mg in healthy Chinese volunteers was 1063 ± 460 ng/mL.5

Volume of distribution

There is limited information on the volume of distribution of benzonatate.

Protein binding

There is limited information on the protein binding profile of benzonatate.


Benzonatate is hydrolyzed to the major metabolite 4-(butylamino)benzoic acid (BABA) by plasma butyrylcholinesterase (BChE).2

Route of elimination

There is limited information on the route of elimination of benzonatate.

Half life

The half life of benzonatate following oral administration of 100 mg in healthy Chinese volunteers was 1.01 ± 0.41 h.5


There is limited information on the clearance of benzonatate.


The lowest published toxic dose (TDLo) from oral administration in man is 51 mg/kg. The oral LD50 is 400 mg/kg and the subcutaneous LD50 is 100 mg/kg in mice.8

The signs and symptoms of overdose are typically observed within 15 to 20 minutes and can lead to neurological and cardiovascular toxicity, which is related to blocked sodium channels. Intentional and unintentional death from overdose may occur. The risk of overdose is highest in children and toxicity may result from the ingestion of 1 or 2 capsules in this age group.3 If capsules are chewed or dissolved in the mouth, oropharyngeal anesthesia will develop rapidly, which may cause choking and a compromised airway function. Symptoms arising from CNS stimulation include restlessness and tremors, which may lead to clonic convulsions followed by profound CNS depression. Within 1 hour following ingestion, convulsions, coma, cerebral edema and cardiac arrest leading to death have been reported.7

Evacuation of gastric contents and administration of copious amounts of activated charcoal is advised. It is important to note that cough and gag reflexes may be significantly depressed even in conscious patients with overdose; special attention is needed to protect against aspiration of gastric contents. When intravenously administering short-acting barbiturates to treat convulsions, the dose should be carefully titrated for the smallest effective dose. Overdose should be managed with supportive care with continuous monitoring of neurologic and cardiovascular status. Intensive support of respiration and cardiovascular-renal function should be initiated for severe intoxication.7 Because benzonatate is structurally similar to local anesthetic agents, the use of intravenous lipid emulsion therapy in response to life-threatening cardiovascular collapse is also suggested.3

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


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.
No interactions found.
Food Interactions
  • Take with or without food. The absorption is unaffected by food.


Synthesis Reference

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

General References
  1. Dicpinigaitis PV, Gayle YE, Solomon G, Gilbert RD: Inhibition of cough-reflex sensitivity by benzonatate and guaifenesin in acute viral cough. Respir Med. 2009 Jun;103(6):902-6. doi: 10.1016/j.rmed.2008.12.008. Epub 2009 Jan 1. [PubMed:19121573]
  2. Bishop-Freeman SC, Shonsey EM, Friederich LW, Beuhler MC, Winecker RE: Benzonatate Toxicity: Nothing to Cough At. J Anal Toxicol. 2017 Jun 1;41(5):461-463. doi: 10.1093/jat/bkx021. [PubMed:28334901]
  3. 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]
  4. Burns JM, Boyer EW: Antitussives and substance abuse. Subst Abuse Rehabil. 2013 Nov 6;4:75-82. doi: 10.2147/SAR.S36761. eCollection 2013. [PubMed:24648790]
  5. Man J, Jiao F, Wang Y, Gu Y, Ding L, Shu C: Determination of benzonatate and its metabolite in human plasma by HPLC-MS/MS: A preliminary pharmacokinetic study in healthy Chinese volunteers after oral administration of benzonatate soft capsule. J Pharm Biomed Anal. 2019 Sep 5;173:134-143. doi: 10.1016/j.jpba.2019.05.030. Epub 2019 May 16. [PubMed:31129533]
  6. Polverino M, Polverino F, Fasolino M, Ando F, Alfieri A, De Blasio F: Anatomy and neuro-pathophysiology of the cough reflex arc. Multidiscip Respir Med. 2012 Jun 18;7(1):5. doi: 10.1186/2049-6958-7-5. [PubMed:22958367]
  7. FDA Approved Drug Products: TESSALON (benzonatate) Perle and Capsule [Link]
  8. Cayman Chemical: Benzonatate MSDS [Link]
External Links
Human Metabolome Database
PubChem Compound
PubChem Substance
Therapeutic Targets Database
RxList Drug Page Drug Page
ATC Codes
R05DB01 — Benzonatate

Clinical Trials

Clinical Trials
1CompletedBasic ScienceCoughing1
1CompletedBasic ScienceHealthy Volunteers1


  • Banner pharmacaps inc
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  • Ethex Corp.
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  • Heartland Repack Services LLC
  • Inwood Labs
  • IVC Industries Inc.
  • Kaiser Foundation Hospital
  • KV Pharmaceutical Co.
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  • Mallinckrodt Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • Patient First Corp.
  • PD-Rx Pharmaceuticals Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Pharmaceutics International Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Pliva Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prescript Pharmaceuticals
  • Provident Pharmaceuticals LLC
  • Qualitest
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Stat Rx Usa
  • Stat Scripts LLC
  • Swiss Caps Ag
  • United Research Laboratories Inc.
  • Vangard Labs Inc.
  • Zydus Pharmaceuticals
Dosage forms
CapsuleOral100 mg/1
CapsuleOral200 mg/1
Capsule, gelatin coatedOral200 mg/1
Capsule, liquid filledOral100 mg/1
Capsule, liquid filledOral200 mg/1
TabletOral100 mg/1
CapsuleOral150 mg/1
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.
Not Available


Experimental Properties
logP2.45HANSCH,C ET AL. (1995)
Predicted Properties
Water Solubility0.00159 mg/mLALOGPS
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
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
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
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)


Mass Spec (NIST)
Not Available
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


This compound belongs to the class of organic compounds known as benzoic acid esters. These are ester derivatives of benzoic acid.
Organic compounds
Super 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
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)


Pharmacological action
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
Uniprot ID
Uniprot Name
Sodium channel protein type 5 subunit alpha
Molecular Weight
226937.475 Da
  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]
  2. Bishop-Freeman SC, Shonsey EM, Friederich LW, Beuhler MC, Winecker RE: Benzonatate Toxicity: Nothing to Cough At. J Anal Toxicol. 2017 Jun 1;41(5):461-463. doi: 10.1093/jat/bkx021. [PubMed:28334901]


Pharmacological action
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
Uniprot ID
Uniprot Name
Molecular Weight
68417.575 Da
  1. Bishop-Freeman SC, Shonsey EM, Friederich LW, Beuhler MC, Winecker RE: Benzonatate Toxicity: Nothing to Cough At. J Anal Toxicol. 2017 Jun 1;41(5):461-463. doi: 10.1093/jat/bkx021. [PubMed:28334901]

Drug created on June 13, 2005 07:24 / Updated on May 02, 2020 03:22

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