Identification

Name
Triprolidine
Accession Number
DB00427  (APRD00306)
Type
Small Molecule
Groups
Approved
Description

First generation histamine H1 antagonist used in allergic rhinitis; asthma; and urticaria. It is a component of cough and cold medicines. It may cause drowsiness.

Structure
Thumb
Synonyms
  • Tripolidina
  • Triprolidin
  • Triprolidine
  • Triprolidinum
Product Ingredients
IngredientUNIICASInChI Key
Triprolidine hydrochlorideNG7A104R3J550-70-9WYUYEJNGHIOFOC-NWBUNABESA-N
Triprolidine hydrochloride monohydrateYAN7R5L8906138-79-0CUZMOIXUFHOLLN-UMVVUDSKSA-N
Product Images
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
HistexTablet, chewable1.25 mg/1OralAllegis Pharmaceuticals, LLC2017-07-24Not applicableUs
HistexSyrup2.5 mg/5mLOralAllegis Pharmaceuticals, LLC2014-03-04Not applicableUs
HISTEX PD DropsSyrup.938 mg/mLOralAllegis Pharmaceuticals, LLC2014-03-06Not applicableUs
HISTEX PDX DropsSyrup1.25 mg/mLOralAllegis Pharmaceuticals, LLC2017-06-22Not applicableUs
M-Hist PDLiquid.625 mg/mLOralMethod Pharmaceuticals2016-11-08Not applicableUs
Triprolidine HydrochlorideLiquid.625 mg/mLOralWoodward Pharma Services Llc2016-10-10Not applicableUs
VanaClear PDLiquid.313 mg/mLOralGm Pharmaceuticals2016-04-04Not applicableUs
Vanahist PdLiquid.625 mg/mLOralGm Pharmaceuticals2014-03-19Not applicableUs
International/Other Brands
Anmin (AND) / Venen (Sato Seiyaku)
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Actifed DM SyrupTriprolidine hydrochloride (1.25 mg) + Dextromethorphan hydrobromide (15 mg) + Pseudoephedrine hydrochloride (30 mg)SyrupOralWarner Lambert Canada Inc.Not applicableNot applicableCanada
Actifed DM SyrupTriprolidine hydrochloride (1.25 mg) + Dextromethorphan hydrobromide (15 mg) + Pseudoephedrine hydrochloride (30 mg)SyrupOralGlaxo Wellcome1980-12-312000-08-03Canada
Actifed DM TabletsTriprolidine hydrochloride (2.5 mg) + Dextromethorphan hydrobromide (30 mg) + Pseudoephedrine hydrochloride (60 mg)TabletOralGlaxo Wellcome1994-12-312000-08-03Canada
Actifed DM TabletsTriprolidine hydrochloride (2.5 mg) + Dextromethorphan hydrobromide (30 mg) + Pseudoephedrine hydrochloride (60 mg)TabletOralWarner Lambert Canada Inc.Not applicableNot applicableCanada
Actifed Plus CapletTriprolidine hydrochloride (2.5 mg) + Acetaminophen (500 mg) + Pseudoephedrine hydrochloride (60 mg)TabletOralGlaxo Wellcome1991-12-312000-08-03Canada
Actifed Plus CapletsTriprolidine hydrochloride (2.5 mg) + Acetaminophen (500 mg) + Pseudoephedrine hydrochloride (60 mg)TabletOralMcneil Consumer Healthcare Division Of Johnson & Johnson Inc2000-04-142016-01-22Canada
Actifed SyrupTriprolidine hydrochloride (1.25 mg) + Pseudoephedrine hydrochloride (30 mg)LiquidOralGlaxo Wellcome1960-12-312000-08-03Canada
Actifed TabletsTriprolidine hydrochloride (2.5 mg) + Pseudoephedrine hydrochloride (60 mg)TabletOralGlaxo Wellcome1960-12-312000-08-03Canada
Actifed TabletsTriprolidine hydrochloride (2.5 mg) + Pseudoephedrine hydrochloride (60 mg)TabletOralMcneil Consumer Healthcare Division Of Johnson & Johnson Inc1999-12-222016-01-22Canada
AprodineTriprolidine hydrochloride (2.5 mg/1) + Pseudoephedrine hydrochloride (60 mg/1)Tablet, film coatedOralRebel Distributors1993-01-09Not applicableUs
Categories
UNII
2L8T9S52QM
CAS number
486-12-4
Weight
Average: 278.3914
Monoisotopic: 278.178298714
Chemical Formula
C19H22N2
InChI Key
CBEQULMOCCWAQT-WOJGMQOQSA-N
InChI
InChI=1S/C19H22N2/c1-16-7-9-17(10-8-16)18(19-6-2-3-12-20-19)11-15-21-13-4-5-14-21/h2-3,6-12H,4-5,13-15H2,1H3/b18-11+
IUPAC Name
2-[(1E)-1-(4-methylphenyl)-3-(pyrrolidin-1-yl)prop-1-en-1-yl]pyridine
SMILES
CC1=CC=C(C=C1)C(=C/CN1CCCC1)\C1=CC=CC=N1

Pharmacology

Indication

For the symptomatic relief of seasonal or perennial allergic rhinitis or nonallergic rhinitis; allergic conjunctivitis; and mild, uncomplicated allergic skin manifestations of urticaria and angioedema. Also used in combination with other agents for the symptomatic relief of symptoms associated with the common cold.

Structured Indications
Pharmacodynamics

In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Triprolidine, is a histamine H1 antagonist that competes with histamine for the normal H1-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies. Triprolidine has anticholinergic and sedative effects.

Mechanism of action

Triprolidine binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Human
Absorption

Rapidly absorbed in the intestinal tract.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

4 to 6 hours.

Clearance
Not Available
Toxicity

Symptoms of overdose include drowsiness, weakness, inco-ordination, difficulty with micturition, respiratory depression, hypotension, agitation, irritability, convulsions, hypertension, palpitation and tachycardia.

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

Interactions

Drug Interactions
DrugInteractionDrug group
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative activities of Triprolidine.Experimental, Illicit
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative activities of Triprolidine.Experimental
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative activities of Triprolidine.Experimental, Illicit
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative activities of Triprolidine.Experimental, Illicit
AmphetamineAmphetamine may decrease the sedative activities of Triprolidine.Approved, Illicit
BenzphetamineBenzphetamine may decrease the sedative activities of Triprolidine.Approved, Illicit
Benzylpenicilloyl PolylysineTriprolidine may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.Approved
BetahistineThe therapeutic efficacy of Betahistine can be decreased when used in combination with Triprolidine.Approved
ChlorphentermineChlorphentermine may decrease the sedative activities of Triprolidine.Illicit, Withdrawn
DextroamphetamineDextroamphetamine may decrease the sedative activities of Triprolidine.Approved, Illicit
DiethylpropionDiethylpropion may decrease the sedative activities of Triprolidine.Approved, Illicit
FesoterodineThe serum concentration of the active metabolites of Fesoterodine can be increased when Fesoterodine is used in combination with Triprolidine.Approved
GepefrineGepefrine may decrease the sedative activities of Triprolidine.Experimental
HyaluronidaseThe therapeutic efficacy of Hyaluronidase can be decreased when used in combination with Triprolidine.Approved, Investigational
HydroxyamphetamineHydroxyamphetamine may decrease the sedative activities of Triprolidine.Approved
Iofetamine I-123Iofetamine I-123 may decrease the sedative activities of Triprolidine.Approved
LisdexamfetamineLisdexamfetamine may decrease the sedative activities of Triprolidine.Approved, Investigational
MephedroneMephedrone may decrease the sedative activities of Triprolidine.Investigational
MephentermineMephentermine may decrease the sedative activities of Triprolidine.Approved
MethamphetamineMethamphetamine may decrease the sedative activities of Triprolidine.Approved, Illicit
MethoxyphenamineMethoxyphenamine may decrease the sedative activities of Triprolidine.Experimental
MetoprololThe serum concentration of Metoprolol can be increased when it is combined with Triprolidine.Approved, Investigational
MidomafetamineMidomafetamine may decrease the sedative activities of Triprolidine.Experimental, Illicit, Investigational
MMDAMMDA may decrease the sedative activities of Triprolidine.Experimental, Illicit
PhenterminePhentermine may decrease the sedative activities of Triprolidine.Approved, Illicit
PseudoephedrinePseudoephedrine may decrease the sedative activities of Triprolidine.Approved
RitobegronRitobegron may decrease the sedative activities of Triprolidine.Investigational
ThioridazineThe serum concentration of Thioridazine can be increased when it is combined with Triprolidine.Approved, Withdrawn
Food Interactions
Not Available

References

General References
  1. Mann KV, Crowe JP, Tietze KJ: Nonsedating histamine H1-receptor antagonists. Clin Pharm. 1989 May;8(5):331-44. [PubMed:2568212]
  2. Simons FE: H1-receptor antagonists. Comparative tolerability and safety. Drug Saf. 1994 May;10(5):350-80. [PubMed:7913608]
  3. Paton DM, Webster DR: Clinical pharmacokinetics of H1-receptor antagonists (the antihistamines). Clin Pharmacokinet. 1985 Nov-Dec;10(6):477-97. [PubMed:2866055]
  4. Telekes A, Holland RL, Withington DA, Peck AW: Effects of triprolidine and dipipanone in the cold induced pain test, and the central nervous system of healthy volunteers. Br J Clin Pharmacol. 1987 Jul;24(1):43-50. [PubMed:3620284]
External Links
Human Metabolome Database
HMDB0014571
KEGG Drug
D01782
PubChem Compound
5282443
PubChem Substance
46505403
ChemSpider
4445597
BindingDB
50292411
ChEBI
84116
ChEMBL
CHEMBL855
Therapeutic Targets Database
DAP001065
PharmGKB
PA451797
IUPHAR
1228
Guide to Pharmacology
GtP Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Triprolidine
ATC Codes
R06AX07 — Triprolidine
MSDS
Download (72.7 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Glaxosmithkline
  • Usl pharma inc
  • Alpharma us pharmaceuticals division
  • Halsey drug co inc
  • Pharmaceutical assoc inc div beach products
  • Vitarine pharmaceuticals inc
  • Watson laboratories inc
Packagers
Dosage forms
FormRouteStrength
TabletOral
Tablet, film coatedOral
Tablet, coatedOral
SyrupOral2.5 mg/5mL
Tablet, chewableOral1.25 mg/1
SyrupOral
SyrupOral.938 mg/mL
SyrupOral1.25 mg/mL
LiquidOral
LiquidOral.625 mg/mL
LiquidOral.313 mg/mL
Prices
Unit descriptionCostUnit
Triprolidine hcl crystals40.33USD g
Triprolidine 1.25 mg/5 ml liq0.15USD ml
Tripohist 1.25 mg/5 ml liquid0.14USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)60 °CPhysProp
water solubility74.9 mg/LNot Available
logP3.92HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0537 mg/mLALOGPS
logP4.14ALOGPS
logP4.05ChemAxon
logS-3.7ALOGPS
pKa (Strongest Basic)8.64ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area16.13 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity98.53 m3·mol-1ChemAxon
Polarizability33.09 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9905
Blood Brain Barrier+0.9664
Caco-2 permeable-0.5814
P-glycoprotein substrateSubstrate0.6644
P-glycoprotein inhibitor IInhibitor0.8311
P-glycoprotein inhibitor IINon-inhibitor0.6624
Renal organic cation transporterInhibitor0.8612
CYP450 2C9 substrateNon-substrate0.8143
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.6075
CYP450 1A2 substrateNon-inhibitor0.8613
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8598
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.9551
BiodegradationNot ready biodegradable0.9833
Rat acute toxicity2.7123 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.7001
hERG inhibition (predictor II)Non-inhibitor0.5557
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-MSsplash10-0a4i-2690000000-a4b47440bb135b0a9add
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as styrenes. These are organic compounds containing an ethenylbenzene moiety.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Styrenes
Direct Parent
Styrenes
Alternative Parents
Toluenes / Pyridines and derivatives / N-alkylpyrrolidines / Heteroaromatic compounds / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Styrene / Toluene / Pyridine / N-alkylpyrrolidine / Pyrrolidine / Heteroaromatic compound / Tertiary aliphatic amine / Tertiary amine / Organoheterocyclic compound / Azacycle
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
pyridines, olefinic compound, N-alkylpyrrolidine (CHEBI:84116)

Targets

Details
1. Histamine H1 receptor
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. Peroutka SJ, Snyder SH: Two distinct serotonin receptors: regional variations in receptor binding in mammalian brain. Brain Res. 1981 Mar 16;208(2):339-47. [PubMed:7214150]
  2. Claro E, Arbones L, Garcia A, Picatoste F: Phosphoinositide hydrolysis mediated by histamine H1-receptors in rat brain cortex. Eur J Pharmacol. 1986 Apr 16;123(2):187-96. [PubMed:3011460]
  3. Kuzmin AI, Zaretsky DV, Kalenikova EI, Zaretskaja MV, Medvedev OS, Chazov EI: The effect of histamine receptor antagonists on stress-induced catecholamine secretion: an adrenomedullary microdialysis study in the rat. Eur J Pharmacol. 1999 Aug 13;378(3):311-6. [PubMed:10493107]
  4. Ziganshina LE, Ziganshin AU, Hoyle CH, Burnstock G: Acute paw oedema formation induced by ATP: re-evaluation of the mechanisms involved. Inflamm Res. 1996 Feb;45(2):96-102. [PubMed:8907591]
  5. Hiroi T, Ohishi N, Imaoka S, Yabusaki Y, Fukui H, Funae Y: Mepyramine, a histamine H1 receptor antagonist, inhibits the metabolic activity of rat and human P450 2D forms. J Pharmacol Exp Ther. 1995 Feb;272(2):939-44. [PubMed:7853212]
  6. Estelle F, Simons R: H1-receptor antagonists: safety issues. Ann Allergy Asthma Immunol. 1999 Nov;83(5):481-8. [PubMed:10582735]
  7. Mann KV, Crowe JP, Tietze KJ: Nonsedating histamine H1-receptor antagonists. Clin Pharm. 1989 May;8(5):331-44. [PubMed:2568212]
  8. Simons FE: H1-receptor antagonists. Comparative tolerability and safety. Drug Saf. 1994 May;10(5):350-80. [PubMed:7913608]
  9. Paton DM, Webster DR: Clinical pharmacokinetics of H1-receptor antagonists (the antihistamines). Clin Pharmacokinet. 1985 Nov-Dec;10(6):477-97. [PubMed:2866055]
  10. 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
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 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 January 19, 2018 10:47