Identification
- Summary
Pentoxyverine is a medication used to suppress a cough in the common cold, flu, bronchitis, and sinusitis.
- Generic Name
- Pentoxyverine
- DrugBank Accession Number
- DB11186
- Background
Pentoxyverine, also referred to as carbetapentane, is a non-opioid central acting antitussive with antimuscarinic, anticonvulsant 4, and local anesthetic properties. It is an active ingredient in over-the-counter cough suppressants in combination with guaifenesin and H1-receptor antagonists 1. Pentoxyverine acts on sigma-1 receptors, as well as kappa and mu-opioid receptors.
The FDA withdrew the use of all oral gel drug products containing pentoxyverine citrate.9 Other forms of pentoxyverine citrate continue to be marketed.
- Type
- Small Molecule
- Groups
- Approved, Investigational, Withdrawn
- Structure
Structure for Pentoxyverine (DB11186)
- Weight
- Average: 333.472
Monoisotopic: 333.230393862 - Chemical Formula
- C20H31NO3
- Synonyms
- Carbetapentane
- Pentoxyverine
Pharmacology
- Indication
Indicated as a cough suppressant to relieve cough caused by the common cold, flu, bronchitis, and sinusitis 1.
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 for symptomatic treatment of Bronchial irritation Combination Product in combination with: Guaifenesin (DB00874), Potassium guaiacolsulfonate (DB13735), Diphenhydramine (DB01075) •••••••••••• ••••• Used in combination for symptomatic treatment of Bronchial irritation Combination Product in combination with: Guaifenesin (DB00874), Diphenhydramine (DB01075), Potassium guaiacolsulfonate (DB13735) •••••••••••• ••••• Used in combination for symptomatic treatment of Coughing Combination Product in combination with: Potassium guaiacolsulfonate (DB13735), Guaifenesin (DB00874), Diphenhydramine (DB01075) •••••••••••• ••••• Symptomatic treatment of Coughing ••• ••• •••••••• Used in combination for symptomatic treatment of Throat irritation Combination Product in combination with: Guaifenesin (DB00874), Potassium guaiacolsulfonate (DB13735), Diphenhydramine (DB01075) •••••••••••• ••••• - Contraindications & Blackbox Warnings
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Pentoxyverine induces an antitussive action. In animal studies, intraperitoneal administration of pentoxyverine inhibited citric-acid-induced cough in guinea-pigs in vivo 2. Some mice and rat studies suggest that pentoxyverine may also exert anticonvulsant activities without inducing a protective effect from NMDA-induced lethality 4,5. Protective effects against maximal electroshock-induced seizures in a dose-related fashion was also observed following either intraperitoneal or oral administration 5. In hERG-transfected cells, pentoxyverine inhibited the outward current of the hERG ion channel with half-maximal inhibition concentrations (IC50) of 3.0 µM 3. In rats receiving intrathecal administration, pentoxyverine exhibited dose-dependent spinal blockade with a more sensory-selective action over motor blockade 6. It induced a spinal blockade with a more sensory/nociceptive-selective action over motor blockade compared to lidocaine 6.
- Mechanism of action
While the mechanism of antitussive action of pentoxyverine is not fully understood, it is thought to be mediated via sigma-1 receptors expressed in the central nervous system 1. Pentoxyverine acts as an agonist at sigma receptors with the Ki of 75±28 nM, as demonstrated in a competitive binding assay 2. The function of sigma receptors on cough suppressant activities is unclear, however these receptors are highly expressed in the nucleus tractus solitarius (NTS) of the brainstem where the afferent fibres first synapse 2. NTS is located very close to the cough centre in the brainstem thus may function as a ‘gate' for the cough reflex and allow sigma-1 receptor agonists to modulate afferent activity prior to reaching the cough center 2. It is suggested that highly lipophilic sigma-1 agonists may penetrate the CNS following systemic administration. When administered as aerosols, sigma-1 receptor agonists may temporarily act in the periphery to modulate cough by acting activate sigma receptors expressed in the lungs 2. However there is limited evidence of peripheral localization of the sigma agonists following aerosol administration and the ruling out of systemic exposure 2. The local anesthesia action of pentoxyverine may occur through inhibition of voltage-gated Na(+) currents 6.
Target Actions Organism ASigma non-opioid intracellular receptor 1 agonistHumans UPotassium voltage-gated channel subfamily H member 2 inhibitorHumans UVoltage-gated sodium channel alpha subunit inhibitorHumans UKappa-type opioid receptor agonistHumans UMu-type opioid receptor antagonistHumans - Absorption
In humans, maximum plasma concentrations are achieved 1.2 hours after oral dosing 1.
- Volume of distribution
No pharmacokinetic data available.
- Protein binding
No pharmacokinetic data available.
- Metabolism
No pharmacokinetic data available.
- Route of elimination
No pharmacokinetic data available.
- Half-life
The half-life is 2.3 hours following oral dosing 1.
- Clearance
No pharmacokinetic data available.
- Adverse Effects
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Acute oral LD50 is 810 mg/kg in rat and 230 mg/kg in mouse MSDS.
- 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
- Avoid alcohol. Concomitant use of pentoxyverine with alcohol may cause additive CNS depressant effects.
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 Pentoxyverine citrate 4SH0MFJ5HJ 23142-01-0 AKJDEXBCRLOVTH-UHFFFAOYSA-N Pentoxyverine tannate 23K1F351T7 1406-98-0 LILZIIRVLKMYCP-HBNMXAOGSA-N - Product Images
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image GAYABEN 150 ML SURUP Pentoxyverine citrate (8.3 mg) + Diphenhydramine hydrochloride (10 mg) + Guaifenesin (100 mg) + Potassium guaiacolsulfonate (133.3 mg) Syrup Oral BİLİM İLAÇ SAN. VE TİC. A.Ş. 1968-07-29 Not applicable Turkey 
Pancold A Pentoxyverine citrate (15 mg/30mL) + Acetaminophen (300 mg/30mL) + Caffeine (30 mg/30mL) + Chlorpheniramine maleate (2.5 mg/30mL) + Guaifenesin (80 mg/30mL) + Phenylephrine hydrochloride (10 mg/30mL) Liquid Oral DONGWHA PHARM. CO. LTD. 2023-07-01 Not applicable US 
Vicks Cough Syrup New Improved Pentoxyverine citrate (15 mg / 15 mL) + Ephedrine (8 mg / 15 mL) + Guaifenesin (200 mg / 15 mL) Syrup Oral Richardson Vicks, Division Of The Procter & Gamble Company 1983-12-31 2000-07-28 Canada 
พี.ดี.คัฟ แคปซูล Pentoxyverine (10 MG) + Dextromethorphan (10 MG) + Guaifenesin (50 MG) Capsule บริษัท ไทย พี ดี เคมีคอล จำกัด จำกัด 1985-06-29 Not applicable Thailand 
- Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image C-Tanna 12D Suspension Pentoxyverine tannate (30 mg/5mL) + Mepyramine tannate (30 mg/5mL) + Phenylephrine tannate (5 mg/5mL) Suspension Oral Prasco, Laboratories 2006-01-01 2008-10-31 US Carbatuss Pentoxyverine citrate (20 mg/5mL) + Guaifenesin (100 mg/5mL) + Phenylephrine hydrochloride (10 mg/5mL) Liquid Oral Gm Pharmaceuticals 2000-11-01 2007-11-01 US Carbetaplex Pentoxyverine citrate (20 mg/5mL) + Guaifenesin (100 mg/5mL) + Phenylephrine hydrochloride (15 mg/5mL) Liquid Oral Breckenridge Pharmaceutical, Inc. 2004-04-01 2009-09-30 US 
Corzall Pentoxyverine citrate (20 mg/5mL) + Pseudoephedrine hydrochloride (30 mg/5mL) Liquid Oral Hawthorn Pharmaceuticals, Inc. 2009-08-27 2011-08-26 US Corzall PE Pentoxyverine citrate (20 mg/5mL) + Dexchlorpheniramine maleate (1 mg/5mL) + Phenylephrine hydrochloride (10 mg/5mL) Liquid Oral Hawthorn Pharmaceuticals, Inc. 2010-09-22 2011-08-26 US
Categories
- ATC Codes
- R05DB05 — Pentoxyverine
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as benzene and substituted derivatives. These are aromatic compounds containing one monocyclic ring system consisting of benzene.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Not Available
- Direct Parent
- Benzene and substituted derivatives
- Alternative Parents
- Trialkylamines / Carboxylic acid esters / Amino acids and derivatives / Monocarboxylic acids and derivatives / Dialkyl ethers / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
- Substituents
- Amine / Amino acid or derivatives / Aromatic homomonocyclic compound / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester / Dialkyl ether / Ether / Hydrocarbon derivative / Monocarboxylic acid or derivatives
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 32C726X12W
- CAS number
- 77-23-6
- InChI Key
- CFJMRBQWBDQYMK-UHFFFAOYSA-N
- InChI
- InChI=1S/C20H31NO3/c1-3-21(4-2)14-15-23-16-17-24-19(22)20(12-8-9-13-20)18-10-6-5-7-11-18/h5-7,10-11H,3-4,8-9,12-17H2,1-2H3
- IUPAC Name
- 2-[2-(diethylamino)ethoxy]ethyl 1-phenylcyclopentane-1-carboxylate
- SMILES
- CCN(CC)CCOCCOC(=O)C1(CCCC1)C1=CC=CC=C1
References
- General References
- Dicpinigaitis PV, Morice AH, Birring SS, McGarvey L, Smith JA, Canning BJ, Page CP: Antitussive drugs--past, present, and future. Pharmacol Rev. 2014 Mar 26;66(2):468-512. doi: 10.1124/pr.111.005116. Print 2014. [Article]
- Brown C, Fezoui M, Selig WM, Schwartz CE, Ellis JL: Antitussive activity of sigma-1 receptor agonists in the guinea-pig. Br J Pharmacol. 2004 Jan;141(2):233-40. doi: 10.1038/sj.bjp.0705605. Epub 2003 Dec 22. [Article]
- Deisemann H, Ahrens N, Schlobohm I, Kirchhoff C, Netzer R, Moller C: Effects of common antitussive drugs on the hERG potassium channel current. J Cardiovasc Pharmacol. 2008 Dec;52(6):494-9. doi: 10.1097/FJC.0b013e31818eec8d. [Article]
- Tortella FC, Musacchio JM: Dextromethorphan and carbetapentane: centrally acting non-opioid antitussive agents with novel anticonvulsant properties. Brain Res. 1986 Sep 24;383(1-2):314-8. [Article]
- Leander JD: Evaluation of dextromethorphan and carbetapentane as anticonvulsants and N-methyl-D-aspartic acid antagonists in mice. Epilepsy Res. 1989 Jul-Aug;4(1):28-33. [Article]
- Leung YM, Tzeng JI, Kuo CS, Chen YW, Chu CC, Wang JJ: The use of carbetapentane for spinal anesthesia and use-dependent block of sodium currents. Eur J Pharmacol. 2013 Aug 15;714(1-3):366-72. doi: 10.1016/j.ejphar.2013.07.013. Epub 2013 Jul 16. [Article]
- Sanofi: Sedotussin (pentoxyverine citrate) oral solution product information [Link]
- AIFA Product Information: Pentossiverina Sanofi (pentoxyverine citrate) oral solution [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
- HMDB0249630
- PubChem Compound
- 2562
- PubChem Substance
- 347827938
- ChemSpider
- 2464
- BindingDB
- 94507
- 20217
- ChEBI
- 94484
- ChEMBL
- CHEMBL73234
- ZINC
- ZINC000003830375
- Wikipedia
- Pentoxyverine
- MSDS
- Download (77.2 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 1 Completed Treatment Healthy Volunteers (HV) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Suspension Oral Solution Oral 1.35 MG/ML Solution Oral 19 MG/ML Liquid Oral Tablet Oral Solution Oral 2.13 mg/ml Solution Oral 30 mg/ml Solution Oral 0.213 % Solution Oral Syrup 135 MG/100ML Tablet, coated Syrup Oral Tablet 15 mg Capsule - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 90-95 MSDS water solubility 1 g/10 ml MSDS - Predicted Properties
Property Value Source Water Solubility 0.0231 mg/mL ALOGPS logP 4.16 ALOGPS logP 3.97 Chemaxon logS -4.2 ALOGPS pKa (Strongest Basic) 9.41 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 38.77 Å2 Chemaxon Rotatable Bond Count 11 Chemaxon Refractivity 97.17 m3·mol-1 Chemaxon Polarizability 39.25 Å3 Chemaxon Number of Rings 2 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
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-001i-0359000000-8426933cbceafa9cfe5b Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-000i-1911000000-1c639c29d11ab6377ad8 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0f8a-3952000000-2b3fb6ea0859f4f5242f Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0017-9601000000-83328a056a6eb3a75d23 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0002-5900000000-562aa1caf1e15b65044c Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0udv-4930000000-1977b9738a61bd9e0a8e 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]- 178.61768 predictedDeepCCS 1.0 (2019) [M+H]+ 180.9757 predictedDeepCCS 1.0 (2019) [M+Na]+ 187.06882 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- Curator comments
- Competitive binding assays finding report the Ki to be 75±28 nM.
- General Function
- Opioid receptor activity
- Specific Function
- Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma m...
- Gene Name
- SIGMAR1
- Uniprot ID
- Q99720
- Uniprot Name
- Sigma non-opioid intracellular receptor 1
- Molecular Weight
- 25127.52 Da
References
- Brown C, Fezoui M, Selig WM, Schwartz CE, Ellis JL: Antitussive activity of sigma-1 receptor agonists in the guinea-pig. Br J Pharmacol. 2004 Jan;141(2):233-40. doi: 10.1038/sj.bjp.0705605. Epub 2003 Dec 22. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- 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
- Deisemann H, Ahrens N, Schlobohm I, Kirchhoff C, Netzer R, Moller C: Effects of common antitussive drugs on the hERG potassium channel current. J Cardiovasc Pharmacol. 2008 Dec;52(6):494-9. doi: 10.1097/FJC.0b013e31818eec8d. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Voltage-gated sodium channel activity
- Specific Function
- 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 protein forms a...
Components:
References
- Leung YM, Tzeng JI, Kuo CS, Chen YW, Chu CC, Wang JJ: The use of carbetapentane for spinal anesthesia and use-dependent block of sodium currents. Eur J Pharmacol. 2013 Aug 15;714(1-3):366-72. doi: 10.1016/j.ejphar.2013.07.013. Epub 2013 Jul 16. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Opioid receptor activity
- Specific Function
- G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synt...
- Gene Name
- OPRK1
- Uniprot ID
- P41145
- Uniprot Name
- Kappa-type opioid receptor
- Molecular Weight
- 42644.665 Da
References
- Kobayashi T, Ikeda K, Ichikawa T, Togashi S, Kumanishi T: Effects of sigma ligands on the cloned mu-, delta- and kappa-opioid receptors co-expressed with G-protein-activated K+ (GIRK) channel in Xenopus oocytes. Br J Pharmacol. 1996 Sep;119(1):73-80. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Voltage-gated calcium channel activity
- Specific Function
- Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone...
- Gene Name
- OPRM1
- Uniprot ID
- P35372
- Uniprot Name
- Mu-type opioid receptor
- Molecular Weight
- 44778.855 Da
References
- Kobayashi T, Ikeda K, Ichikawa T, Togashi S, Kumanishi T: Effects of sigma ligands on the cloned mu-, delta- and kappa-opioid receptors co-expressed with G-protein-activated K+ (GIRK) channel in Xenopus oocytes. Br J Pharmacol. 1996 Sep;119(1):73-80. [Article]
Drug created at December 03, 2015 16:51 / Updated at November 18, 2022 07:07