Identification

Name
Carbinoxamine
Accession Number
DB00748  (APRD00765)
Type
Small Molecule
Groups
Approved
Description

Carbinoxamine is a first generation antihistamine that competes with free histamine for binding at HA-receptor sites. This antagonizes the effects of histamine on HA-receptors, leading to a reduction of the negative symptoms brought on by histamine HA-receptor binding. The product label for carbinoxamine as an over the counter cough and cold medicine is being modified to state "do not use" in children under 4 years of age in order to prevent and reduce misuse, as many unapproved carbinoxamine-containing preparations contained inappropriate labeling, which promoted unapproved uses (including management of congestion, cough, the common cold, and the use in children under 2 years of age), which can potentially cause serious health risks.

Structure
Thumb
Synonyms
  • (+-)-Carbinoxamine
  • {2-[(4-chloro-phenyl)-pyridin-2-yl-methoxy]-ethyl}-dimethyl-amine
  • 2-(P-chloro-alpha-(2-(dimethylamino)Ethoxy)benzyl)pyridine
  • Carbinoxamin
  • Carbinoxamina
  • Carbinoxamine
  • Carbinoxamine base
  • Carbinoxaminum
  • Paracarbinoxamine
Product Ingredients
IngredientUNIICASInChI Key
Carbinoxamine Maleate02O55696WH3505-38-2GVNWHCVWDRNXAZ-BTJKTKAUSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Karbinal ERSuspension, extended release4 mg/5mLOralAvadel Pharmaceuticals (Usa), Inc.2014-01-032018-08-24Us
Karbinal ERSuspension, extended release4 mg/5mLOralZylera Pharmaceuticals, LLC2014-01-03Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ArbinoxaTablet4 mg/1OralHawthorn Pharmaceuticals, Inc.2010-08-232017-10-01Us
ArbinoxaSolution0.8 mg/1mLOralHawthorn Pharmaceuticals, Inc.2011-04-012016-11-18Us
Carbinoxamine MaleateSyrup4 mg/5mLOralCreekwood Pharmaceuticals, Inc.2010-10-272012-10-27Us
Carbinoxamine MaleateTablet4 mg/1OralBreckenridge Pharmaceutical, Inc.2012-12-10Not applicableUs
Carbinoxamine MaleateTablet4 mg/1OralPar Pharmaceutical2008-05-30Not applicableUs
Carbinoxamine MaleateTablet4 mg/1OralRiver’s Edge Pharmaceuticals, LLC2011-12-012011-12-01Us
Carbinoxamine MaleateTablet4 mg/1OralBiocomp Pharma, Inc.2011-05-27Not applicableUs
Carbinoxamine MaleateTablet4 mg/1OralCreekwood Pharmaceuticals, Inc.2010-10-272013-09-17Us
Carbinoxamine MaleateTablet6 mg/1OralMikart, Inc.2016-05-31Not applicableUs
Carbinoxamine MaleateTablet6 mg/1OralFoxland Pharmaceuticals, Inc.2017-12-18Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Carbinoxamine/Pseudoephedrine/DMCarbinoxamine Maleate (1 mg/1mL) + Dextromethorphan hydrobromide monohydrate (4 mg/1mL) + Pseudoephedrine hydrochloride (15 mg/1mL)LiquidOralPhysicians Total Care, Inc.2003-01-152007-08-08Us
Coldec DSCarbinoxamine Maleate (2 mg/5mL) + Pseudoephedrine hydrochloride (25 mg/5mL)SyrupOralBreckenridge Pharmaceutical, Inc.2003-05-012004-03-31Us
Rondamine DMCarbinoxamine Maleate (1 mg/1mL) + Dextromethorphan hydrobromide monohydrate (4 mg/1mL) + Pseudoephedrine hydrochloride (15 mg/1mL)LiquidOralMajor2002-02-052008-05-30Us
International/Other Brands
Allergefon (SERP) / Clistin / Histin (Kenyaku) / Karbinal / Rotoxamine / Satinmin (Shou Chan)
Categories
UNII
982A7M02H5
CAS number
486-16-8
Weight
Average: 290.788
Monoisotopic: 290.118590947
Chemical Formula
C16H19ClN2O
InChI Key
OJFSXZCBGQGRNV-UHFFFAOYSA-N
InChI
InChI=1S/C16H19ClN2O/c1-19(2)11-12-20-16(15-5-3-4-10-18-15)13-6-8-14(17)9-7-13/h3-10,16H,11-12H2,1-2H3
IUPAC Name
{2-[(4-chlorophenyl)(pyridin-2-yl)methoxy]ethyl}dimethylamine
SMILES
CN(C)CCOC(C1=CC=C(Cl)C=C1)C1=CC=CC=N1

Pharmacology

Indication

For symptomatic relief of seasonal and perennial allergic rhinitis and vasomotor rhinitis, as well as allergic conjunctivitis caused by foods and inhaled allergens. Also for the relief of allergic reactions to blood or plasma, and the symptomatic management of mild, uncomplicated allergic skin manifestations of urticaria and angioedema.

Associated Conditions
Pharmacodynamics

Carbinoxamine is a first generation antihistamine of the ethanolamine class. Ethanolamine antihistamines have significant antimuscarinic activity and produce marked sedation in most patients. In addition to the usual allergic symptoms, the drug also treats irritant cough and nausea, vomiting, and vertigo associated with motion sickness. It also is used commonly to treat drug-induced extrapyramidal symptoms as well as to treat mild cases of Parkinson's disease. Rather than preventing the release of histamine, as do cromolyn and nedocromil, carbinoxamine competes with free histamine for binding at HA-receptor sites. Carbinoxamine competitively antagonizes the effects of histamine on HA-receptors in the GI tract, uterus, large blood vessels, and bronchial muscle. Ethanolamine derivatives have greater anticholinergic activity than do other antihistamines, which probably accounts for the antidyskinetic action of carbinoxamine.

Mechanism of action

Carbinoxamine competes with free histamine for binding at HA-receptor sites. This antagonizes the effects of histamine on HA-receptors, leading to a reduction of the negative symptoms brought on by histamine HA-receptor binding. Carbinoxamine's anticholinergic action appears to be due to a central antimuscarinic effect, which also may be responsible for its antiemetic effects, although the exact mechanism is unknown.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

10 to 20 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Carbinoxamine H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Carbinoxamine.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Carbinoxamine.
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative and stimulatory activities of Carbinoxamine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative and stimulatory activities of Carbinoxamine.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative and stimulatory activities of Carbinoxamine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Carbinoxamine.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative and stimulatory activities of Carbinoxamine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Carbinoxamine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Carbinoxamine is combined with 4-Methoxyamphetamine.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Carbinoxamine.
Food Interactions
Not Available

References

Synthesis Reference

Tilford. C.H. and Shelton, R.S.; U.S. Patent 2,606,195;August 5,1952; assigned to The Wm.S. Merrell Company. Swain, A.P.; U.S. Patent 2800,485; July 23,1957; assigned to McNeil Laboratories, Inc.

General References
  1. BEALE HD, RAWLING FF, FIGLEY KD: Clistin maleate; a clinical appraisal of a new antihistaminic. J Allergy. 1954 Nov;25(6):521-4. [PubMed:13211145]
External Links
Human Metabolome Database
HMDB0014886
KEGG Compound
C06871
PubChem Compound
2564
PubChem Substance
46506787
ChemSpider
2466
BindingDB
81464
ChEBI
3398
ChEMBL
CHEMBL864
Therapeutic Targets Database
DAP001069
PharmGKB
PA164746898
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Carbinoxamine
ATC Codes
R06AA08 — Carbinoxamine
MSDS
Download (74.6 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Mcneil pharmaceutical co div mcneilab inc
  • Boca pharmacal inc
  • Cypress pharmaceutical inc
  • Mikart inc
  • Invagen pharmaceuticals inc
  • Ortho mcneil pharmaceutical inc
Packagers
  • Boca Pharmacal
  • Breckenridge Pharmaceuticals
  • Great Southern Laboratories
  • Mikart Inc.
  • Pamlab LLC
  • Pan American
  • Physicians Total Care Inc.
  • Scientific Laboratories Inc.
  • Sovereign Pharmaceuticals Ltd.
  • Teamm Pharmaceuticals Inc.
  • Tri Med Laboratories Inc.
  • Zerxis Pharmaceuticals
  • Zyber Pharmaceuticals
Dosage forms
FormRouteStrength
SolutionOral0.8 mg/1mL
SolutionOral4 mg/5mL
SyrupOral4 mg/5mL
TabletOral4 mg/1
SyrupOral
Suspension, extended releaseOral4 mg/5mL
LiquidOral
TabletOral6 mg/1
Prices
Unit descriptionCostUnit
Palgic 4 mg tablet0.87USD tablet
Carbinoxamine maleate 4 mg tablet0.65USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8062667No2009-03-292029-03-29Us
US9522191No2007-06-152027-06-15Us

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)< 25 °CPhysProp
boiling point (°C)160 °C at 1.00E-01 mm HgPhysProp
logP2.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.228 mg/mLALOGPS
logP3.03ALOGPS
logP3.27ChemAxon
logS-3.1ALOGPS
pKa (Strongest Basic)8.87ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area25.36 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity82.13 m3·mol-1ChemAxon
Polarizability31.7 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9787
Blood Brain Barrier+0.955
Caco-2 permeable+0.7503
P-glycoprotein substrateSubstrate0.6804
P-glycoprotein inhibitor INon-inhibitor0.5997
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterInhibitor0.7956
CYP450 2C9 substrateNon-substrate0.8203
CYP450 2D6 substrateSubstrate0.5558
CYP450 3A4 substrateSubstrate0.6473
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8452
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8403
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5557
Ames testNon AMES toxic0.8751
CarcinogenicityNon-carcinogens0.9182
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.9003 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7085
hERG inhibition (predictor II)Inhibitor0.6835
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
GC-MS Spectrum - EI-BGC-MSsplash10-0ab9-9000000000-a413c068c7a879eb2068
Mass Spectrum (Electron Ionization)MSsplash10-0ab9-9200000000-c3abf61d5cdaa81de77d
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
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0uxr-0490000000-9ece1371a4992f21aa52

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzylethers. These are aromatic ethers with the general formula ROCR' (R = alkyl, aryl; R'=benzene).
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzylethers
Direct Parent
Benzylethers
Alternative Parents
Chlorobenzenes / Pyridines and derivatives / Aryl chlorides / Heteroaromatic compounds / Trialkylamines / Dialkyl ethers / Azacyclic compounds / Organopnictogen compounds / Organochlorides / Hydrocarbon derivatives
Substituents
Benzylether / Chlorobenzene / Halobenzene / Aryl chloride / Aryl halide / Pyridine / Heteroaromatic compound / Tertiary aliphatic amine / Tertiary amine / Dialkyl ether
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
tertiary amino compound, pyridines, monochlorobenzenes (CHEBI:3398)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Histamine receptor activity
Specific Function
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. Oishi R, Shishido S, Yamori M, Saeki K: Comparison of the effects of eleven histamine H1-receptor antagonists on monoamine turnover in the mouse brain. Naunyn Schmiedebergs Arch Pharmacol. 1994 Feb;349(2):140-4. [PubMed:7513381]
  2. Ramadan AA, Mandil H: Spectrophotometric determination of carbinoxamine maleate in pharmaceutical formulations by ternary complex formation with Cu(II) and eosin. Anal Biochem. 2006 Jun 1;353(1):133-7. Epub 2006 Mar 9. [PubMed:16574052]
  3. Darby WJ: Nutrition, food needs and technologic priorities: the World Food Conference. Nutr Rev. 1975 Aug;33(8):225-34. [PubMed:1143714]
  4. Yang J, Dudley GB: [1,2]-Anionic rearrangement of 2-benzyloxypyridine and related pyridyl ethers. J Org Chem. 2009 Oct 16;74(20):7998-8000. doi: 10.1021/jo901707x. [PubMed:19761204]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:44