Identification

Name
Diphenylpyraline
Accession Number
DB01146  (APRD00719)
Type
Small Molecule
Groups
Approved, Investigational
Description

Diphenylpyraline is an antihistamine. Antihistamines used in the treatment of allergy act by competing with histamine for H 1-receptor sites on effector cells. Antihistamines prevent, but do not reverse, responses mediated by histamine alone. Antihistamines antagonize, in varying degrees, most of the pharmacological effects of histamine, including urticaria and pruritus.

Structure
Thumb
Synonyms
  • 1-methyl-4-hydroxypiperidine benzhydryl ether
  • 1-methyl-4-piperidyl benzhydryl ether
  • 4-(benzhydryloxy)-1-methylpiperidine
  • 4-(benzhydryloxy)-N-methylpiperidine
  • Difenilpiralina
  • Diphenylpyralamine
  • Diphenylpyraline
  • Diphenylpyralinum
Product Ingredients
IngredientUNIICASInChI Key
Diphenylpyraline hydrochlorideG9FU7F1E87132-18-3LPRLDRXGWKXRMQ-UHFFFAOYSA-N
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Biohisdex DM DecongestantDiphenylpyraline hydrochloride (2 mg) + Dextromethorphan hydrobromide (10 mg) + Phenylephrine hydrochloride (20 mg)LiquidOralEverest Pharmaceuticals Ltd.1979-12-311999-07-14Canada
Biohisdine DM DecongestantDiphenylpyraline hydrochloride (1 mg) + Dextromethorphan hydrobromide (5 mg) + Phenylephrine hydrochloride (10 mg)LiquidOralEverest Pharmaceuticals Ltd.1979-12-311999-07-14Canada
CorytabDiphenylpyraline hydrochloride (2 mg) + Acetaminophen (300 mg) + Caffeine (16 mg)TabletOralLes Laboratoires Vachon Inc.1988-12-312009-02-24Canada
Creo-rectal AdulteDiphenylpyraline hydrochloride (1.5 mg) + Camphor (5 mg) + Guaiacol carbonate (600 mg)SuppositoryRectalSandoz Canada Incorporated1951-12-31Not applicableCanada
Creo-rectal Enfants/childrenDiphenylpyraline hydrochloride (0.5 mg) + Camphor (2 mg) + Guaiacol carbonate (200 mg)SuppositoryRectalSandoz Canada Incorporated1951-12-31Not applicableCanada
Creo-rectal NourrissonDiphenylpyraline hydrochloride (0.25 mg) + Camphor (1 mg) + Guaiacol carbonate (100 mg)SuppositoryRectalSandoz Canada Incorporated1951-12-312012-11-02Canada
Emercidin D TabDiphenylpyraline hydrochloride (2 mg) + Acetaminophen (325 mg) + Caffeine (30 mg) + Phenylpropanolamine hydrochloride (25 mg)TabletOralPharmetics (2011) Inc.1989-12-312001-03-30Canada
Emercreme No4 Ont EfaDiphenylpyraline hydrochloride (2 mg) + Bacitracin (65 unit) + Benzocaine (20 mg) + Cetylpyridinium chloride (.4 mg) + Tyrothricin (1 mg)OintmentTopicalPharmavite Laboratories (1987) Inc.1984-12-31Not applicableCanada
Jamp-cough Suppositories AdultDiphenylpyraline hydrochloride (1.5 mg) + Camphor (5 mg) + Guaiacol carbonate (600 mg)SuppositoryRectalJamp Pharma CorporationNot applicableNot applicableCanada
Jamp-suppositories ChildrenDiphenylpyraline hydrochloride (0.5 mg) + Camphor (2 mg) + Guaiacol carbonate (200 mg)SuppositoryRectalJamp Pharma CorporationNot applicableNot applicableCanada
International/Other Brands
Allergen / Arbid / Belfene / Diafen (Riker) / Hispril (Nopco) / Histyn / Lergobine / Lyssipoll (Lyssia) / Mepiben / Neargal
Categories
UNII
33361OE3AV
CAS number
147-20-6
Weight
Average: 281.392
Monoisotopic: 281.177964363
Chemical Formula
C19H23NO
InChI Key
OWQUZNMMYNAXSL-UHFFFAOYSA-N
InChI
InChI=1S/C19H23NO/c1-20-14-12-18(13-15-20)21-19(16-8-4-2-5-9-16)17-10-6-3-7-11-17/h2-11,18-19H,12-15H2,1H3
IUPAC Name
4-(diphenylmethoxy)-1-methylpiperidine
SMILES
CN1CCC(CC1)OC(C1=CC=CC=C1)C1=CC=CC=C1

Pharmacology

Indication

For use in the treatment of allergic rhinitis, hay fever, and allergic skin disorders.

Associated Conditions
Pharmacodynamics

Diphenylpyraline is an antihistamine that prevents, but does not reverse, responses mediated by histamine alone. Diphenylpyraline antagonizes most of the pharmacological effects of histamine, including urticaria and pruritus. Also, diphenylpyraline may exhibit anticholinergic actions (as do most of the antihistamines) and may thus provide a drying effect on the nasal mucosa.

Mechanism of action

Antihistamines such as diphenylpyraline used in the treatment of allergy act by competing with histamine for H1-receptor sites on effector cells. This reduces the effects of histamine, leading to a temporary reduction of allergy symptoms.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Human
USodium-dependent dopamine transporter
inhibitor
Human
Absorption

Well absorbed after oral administration.

Volume of distribution
Not Available
Protein binding

> 99% in human serum albumin

Metabolism

Hepatic

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Diphenylpyraline H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative and stimulatory activities of Diphenylpyraline.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative and stimulatory activities of Diphenylpyraline.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative and stimulatory activities of Diphenylpyraline.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative and stimulatory activities of Diphenylpyraline.
AmphetamineAmphetamine may decrease the sedative and stimulatory activities of Diphenylpyraline.
BenzphetamineBenzphetamine may decrease the sedative and stimulatory activities of Diphenylpyraline.
Benzylpenicilloyl PolylysineDiphenylpyraline may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.
BetahistineThe therapeutic efficacy of Betahistine can be decreased when used in combination with Diphenylpyraline.
ChlorphentermineChlorphentermine may decrease the sedative and stimulatory activities of Diphenylpyraline.
DeoxyepinephrineThe therapeutic efficacy of Deoxyepinephrine can be increased when used in combination with Diphenylpyraline.
Food Interactions
Not Available

References

Synthesis Reference

Knox, L.H. and Kapp, R.; U.S. Patent 2,479,843; August 23, 1949; assigned to Nopco Chemical Company.

US2479843
General References
  1. Lapa GB, Mathews TA, Harp J, Budygin EA, Jones SR: Diphenylpyraline, a histamine H1 receptor antagonist, has psychostimulant properties. Eur J Pharmacol. 2005 Jan 4;506(3):237-40. Epub 2004 Dec 8. [PubMed:15627433]
  2. Ohno T, Kobayashi S, Hayashi M, Sakurai M, Kanazawa I: Diphenylpyraline-responsive parkinsonism in cerebrotendinous xanthomatosis: long-term follow up of three patients. J Neurol Sci. 2001 Jan 1;182(2):95-7. [PubMed:11137513]
  3. Puhakka H, Rantanen T, Virolainen E: Diphenylpyraline (Lergobine) in the treatment of patients suffering from allergic and vasomotor rhinitis. J Int Med Res. 1977;5(1):37-41. [PubMed:14039]
External Links
Human Metabolome Database
HMDB0015277
KEGG Drug
D07862
PubChem Compound
3103
PubChem Substance
46504936
ChemSpider
2992
BindingDB
50241333
ChEBI
59788
ChEMBL
CHEMBL1492
Therapeutic Targets Database
DAP001071
PharmGKB
PA164746377
Wikipedia
Diphenylpyraline
ATC Codes
R06AA57 — Diphenylpyraline, combinationsR06AA07 — Diphenylpyraline

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2Unknown StatusTreatmentAllergic Rhinitis (AR) / Asthma Bronchial / Conjunctivitis, Seasonal Allergic1
Not AvailableRecruitingBasic ScienceImmunologic Desensitization1
Not AvailableTerminatedTreatmentAllergic Rhinitis (AR)1
Not AvailableUnknown StatusDiagnosticBirch Pollen Allergy / Healthy Control Subjects1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
LiquidOral
SuppositoryRectal
OintmentTopical
SyrupOral
TabletOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)206Not Available
logP3.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0188 mg/mLALOGPS
logP3.82ALOGPS
logP3.66ChemAxon
logS-4.2ALOGPS
pKa (Strongest Basic)8.87ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area12.47 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity87.36 m3·mol-1ChemAxon
Polarizability32.97 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9896
Blood Brain Barrier+0.9912
Caco-2 permeable+0.8103
P-glycoprotein substrateSubstrate0.7232
P-glycoprotein inhibitor IInhibitor0.6457
P-glycoprotein inhibitor IINon-inhibitor0.96
Renal organic cation transporterInhibitor0.8556
CYP450 2C9 substrateNon-substrate0.7922
CYP450 2D6 substrateSubstrate0.5316
CYP450 3A4 substrateSubstrate0.5729
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.9492
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9468
Ames testNon AMES toxic0.7893
CarcinogenicityNon-carcinogens0.9481
BiodegradationNot ready biodegradable0.9066
Rat acute toxicity2.3662 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.8094
hERG inhibition (predictor II)Inhibitor0.5695
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-MSsplash10-0002-9500000000-c0c4dde4b9a2e2daa726
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 diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Diphenylmethanes
Direct Parent
Diphenylmethanes
Alternative Parents
Benzylethers / Piperidines / Trialkylamines / Dialkyl ethers / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Diphenylmethane / Benzylether / Piperidine / Tertiary aliphatic amine / Tertiary amine / Azacycle / Organoheterocyclic compound / Ether / Dialkyl ether / Hydrocarbon derivative
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
piperidines, tertiary amine (CHEBI:59788)

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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Nakai T, Kitamura N, Hashimoto T, Kajimoto Y, Nishino N, Mita T, Tanaka C: Decreased histamine H1 receptors in the frontal cortex of brains from patients with chronic schizophrenia. Biol Psychiatry. 1991 Aug 15;30(4):349-56. [PubMed:1912125]
  4. Taniguchi K, Masuda Y, Takanaka K: Inhibitory effects of histamine H1 receptor blocking drugs on metabolic activations of neutrophils. J Pharmacobiodyn. 1991 Feb;14(2):87-93. [PubMed:1678430]
  5. Weis R, Schweiger K, Faist J, Rajkovic E, Kungl AJ, Fabian WM, Schunack W, Seebacher W: Antimycobacterial and H1-antihistaminic activity of 2-substituted piperidine derivatives. Bioorg Med Chem. 2008 Dec 15;16(24):10326-31. doi: 10.1016/j.bmc.2008.10.042. Epub 2008 Oct 22. [PubMed:18977145]
  6. Lapa GB, Mathews TA, Harp J, Budygin EA, Jones SR: Diphenylpyraline, a histamine H1 receptor antagonist, has psychostimulant properties. Eur J Pharmacol. 2005 Jan 4;506(3):237-40. Epub 2004 Dec 8. [PubMed:15627433]
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Monoamine transmembrane transporter activity
Specific Function
Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A3
Uniprot ID
Q01959
Uniprot Name
Sodium-dependent dopamine transporter
Molecular Weight
68494.255 Da
References
  1. Lapa GB, Mathews TA, Harp J, Budygin EA, Jones SR: Diphenylpyraline, a histamine H1 receptor antagonist, has psychostimulant properties. Eur J Pharmacol. 2005 Jan 4;506(3):237-40. Epub 2004 Dec 8. [PubMed:15627433]

Drug created on June 13, 2005 07:24 / Updated on December 14, 2018 12:39