Identification
NameDiphenylpyraline
Accession NumberDB01146  (APRD00719)
TypeSmall Molecule
GroupsApproved
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
Diphenylpyralinum
External IDs Not Available
Product Ingredients
IngredientUNIICASInChI KeyDetails
Diphenylpyraline HydrochlorideG9FU7F1E87 132-18-3LPRLDRXGWKXRMQ-UHFFFAOYSA-NDetails
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AllergenNot Available
ArbidNot Available
BelfeneNot Available
DiafenRiker
HisprilNopco
HistynNot Available
LergobineNot Available
LyssipollLyssia
MepibenNot Available
NeargalNot Available
Brand mixtures
NameLabellerIngredients
Biohisdex DM DecongestantEverest Pharmaceuticals Ltd.
Biohisdine DM DecongestantEverest Pharmaceuticals Ltd.
CorytabLes Laboratoires Vachon Inc.
Creo-rectal AdulteSandoz Canada Incorporated
Creo-rectal Enfants/childrenSandoz Canada Incorporated
Creo-rectal NourrissonSandoz Canada Incorporated
Emercidin D TabPharmetics (2011) Inc.
Emercreme No4 Ont EfaPharmavite Laboratories (1987) Inc.
Jamp-cough Suppositories AdultJamp Pharma Corporation
Jamp-suppositories ChildrenJamp Pharma Corporation
MetrateMedic Laboratory LtÉe
Nezger TabLes Produits Gerbex Inc.
Oradrine 2 TabNutribon (1986) Inc.
Oradrine TabletsPharmavite Laboratories (1987) Inc.
Sinugex 38Frega Inc.
Vito Bronches SiropDuchesnay Inc.
Categories
UNII33361OE3AV
CAS number147-20-6
WeightAverage: 281.392
Monoisotopic: 281.177964363
Chemical FormulaC19H23NO
InChI KeyOWQUZNMMYNAXSL-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.

Structured Indications
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.

TargetKindPharmacological actionActionsOrganismUniProt ID
Histamine H1 receptorProteinyes
antagonist
HumanP35367 details
Sodium-dependent dopamine transporterProteinunknown
inhibitor
HumanQ01959 details
Related Articles
Absorption

Well absorbed after oral administration.

Volume of distributionNot Available
Protein binding

> 99% in human serum albumin

Metabolism

Hepatic

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions Not Available
Food InteractionsNot 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
ATC CodesR06AA57 — Diphenylpyraline, combinationsR06AA07 — Diphenylpyraline
AHFS Codes
  • 92:04.00*
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2Unknown StatusTreatmentAllergic Rhinitis (AR) / Asthma Bronchial / Conjunctivitis, Seasonal Allergic1
Not AvailableActive Not RecruitingDiagnosticAsthma Bronchial / Asthma, Allergic / Non-allergic Asthma1
Not AvailableRecruitingBasic ScienceImmunologic Desensitization1
Not AvailableTerminatedTreatmentAllergic Rhinitis (AR)1
Not AvailableUnknown StatusDiagnosticBirch Pollen Allergy / Healthy Control Subjects1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
LiquidOral
SuppositoryRectal
OintmentTopical
SyrupOral
TabletOral
PricesNot Available
PatentsNot Available
Properties
StateSolid
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
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of chemical entities 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.
KingdomChemical entities
Super ClassOrganic compounds
ClassBenzenoids
Sub ClassBenzene and substituted derivatives
Direct ParentDiphenylmethanes
Alternative ParentsBenzylethers / Piperidines / Trialkylamines / Dialkyl ethers / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
SubstituentsDiphenylmethane / Benzylether / Piperidine / Tertiary aliphatic amine / Tertiary amine / Azacycle / Organoheterocyclic compound / Ether / Dialkyl ether / Hydrocarbon derivative
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptorspiperidines, 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 catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
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 July 18, 2017 16:56