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Identification
NameDiphenidol
Accession NumberDB01231  (APRD00929)
Typesmall molecule
Groupsapproved, withdrawn
Description

Diphenidol is an antiemetic agent used in the treatment of vomiting and vertigo. Diphenidol overdose may result in serious toxicity in children.

Structure
Thumb
Synonyms
SynonymLanguageCode
alpha,alpha-Diphenyl-1-piperidinebutanolNot AvailableNot Available
DifenidolNot AvailableINN
DifenidoloNot AvailableDCIT
DifenidolumLatinINN
DiphenidolNot AvailableNot Available
Diphenyl(3-(1-piperidyl)propyl)carbinolNot AvailableNot Available
Salts
Name/CAS Structure Properties
Diphenidol Hydrochloride
Thumb
  • InChI Key: AVZIYZHXZAYGJS-UHFFFAOYSA-N
  • Monoisotopic Mass: 345.18594223
  • Average Mass: 345.906
DBSALT000395
Brand names
NameCompany
SatanolonTatsumi Kagaku
VertergeNot Available
VontrolSanfer
YesdolNot Available
Brand mixturesNot Available
Categories
CAS number972-02-1
WeightAverage: 309.4452
Monoisotopic: 309.209264491
Chemical FormulaC21H27NO
InChI KeyOGAKLTJNUQRZJU-UHFFFAOYSA-N
InChI
InChI=1S/C21H27NO/c23-21(19-11-4-1-5-12-19,20-13-6-2-7-14-20)15-10-18-22-16-8-3-9-17-22/h1-2,4-7,11-14,23H,3,8-10,15-18H2
IUPAC Name
1,1-diphenyl-4-(piperidin-1-yl)butan-1-ol
SMILES
OC(CCCN1CCCCC1)(C1=CC=CC=C1)C1=CC=CC=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassDiphenylmethanes
Direct parentDiphenylmethanes
Alternative parentsPiperidines; Tertiary Alcohols; Tertiary Amines; Polyamines
Substituentspiperidine; tertiary alcohol; tertiary amine; polyamine; amine; alcohol; organonitrogen compound
Classification descriptionThis compound belongs to the diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
Pharmacology
IndicationFor use in the prevention and symptomatic treatment of peripheral (labyrinthine) vertigo and associated nausea and vomiting that occur in such conditions as Meniere's disease and surgery of the middle and inner ear. Also for the control of nausea and vomiting associated with postoperative states, malignant neoplasms, labyrinthine disturbances, antineoplastic agent therapy, radiation sickness, and infectious diseases.
PharmacodynamicsDiphenidol is used for control of nausea and vomiting. It has an antivertigo effect on the vestibular apparatus, inhibiting the chemoreceptor trigger zone to control nausea and vomiting, thus preventing motion sickness.
Mechanism of actionThe mechanism by which diphenidol exerts its antiemetic and antivertigo effects is not precisely known. It is thought to diminish vestibular stimulation and depress labyrinthine function and as an antimuscarinic agent. An action on the medullary chemoreceptive trigger zone may also be involved in the antiemetic effect. Diphenidol has no significant sedative, tranquilizing, or antihistaminic action. It has a weak peripheral anticholinergic effect.
AbsorptionWell absorbed from gastrointestinal tract following oral administration.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half life4 hours
ClearanceNot Available
ToxicitySymptoms of overdose include drowsiness (severe); shortness of breath or troubled breathing; unusual tiredness or weakness (severe).
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9296
Blood Brain Barrier + 0.9606
Caco-2 permeable + 0.6951
P-glycoprotein substrate Substrate 0.7254
P-glycoprotein inhibitor I Inhibitor 0.5603
P-glycoprotein inhibitor II Non-inhibitor 0.7523
Renal organic cation transporter Inhibitor 0.7647
CYP450 2C9 substrate Non-substrate 0.8378
CYP450 2D6 substrate Non-substrate 0.7102
CYP450 3A4 substrate Non-substrate 0.5631
CYP450 1A2 substrate Non-inhibitor 0.9046
CYP450 2C9 substrate Non-inhibitor 0.9255
CYP450 2D6 substrate Inhibitor 0.9373
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.7862
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9362
Ames test Non AMES toxic 0.8763
Carcinogenicity Non-carcinogens 0.924
Biodegradation Not ready biodegradable 0.9177
Rat acute toxicity 2.6101 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Strong inhibitor 0.6086
hERG inhibition (predictor II) Inhibitor 0.6009
Pharmacoeconomics
Manufacturers
  • Glaxosmithkline
Packagers
  • Professional Co.
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Diphenidol hcl powder32.4USDg
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point212-214Miescher, K. and Marxer, A.; U.S. Patent 2,411,664; November 26, 1946; assigned to Ciba Pharmaceutical Products, Inc.
logP4.3Not Available
Predicted Properties
PropertyValueSource
water solubility5.87e-03 g/lALOGPS
logP4.08ALOGPS
logP4.22ChemAxon
logS-4.7ALOGPS
pKa (strongest acidic)13.4ChemAxon
pKa (strongest basic)9.23ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count1ChemAxon
polar surface area23.47ChemAxon
rotatable bond count6ChemAxon
refractivity96.92ChemAxon
polarizability36.66ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Miescher, K. and Marxer, A.; U.S. Patent 2,411,664; November 26, 1946; assigned to Ciba
Pharmaceutical Products, Inc.

General Reference
  1. Link
External Links
ResourceLink
KEGG DrugD03858
KEGG CompoundC06961
PubChem Compound3055
PubChem Substance46506486
ChemSpider2947
ChEBI4638
ChEMBLCHEMBL936
Therapeutic Targets DatabaseDAP001133
PharmGKBPA164746037
Drugs.comhttp://www.drugs.com/cons/diphenidol.html
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelshow(374 KB)
MSDSshow(73.5 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Muscarinic acetylcholine receptor M1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M1 P11229 Details

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
  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
  3. Waelbroeck M, Camus J, Tastenoy M, Mutschler E, Strohmann C, Tacke R, Lambrecht G, Christophe J: Stereoselectivity of®- and (S)-hexahydro-difenidol binding to neuroblastoma M1, cardiac M2, pancreatic M3, and striatum M4 muscarinic receptors. Chirality. 1991;3(2):118-23. Pubmed

2. Muscarinic acetylcholine receptor M3

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M3 P20309 Details

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
  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
  3. Braverman AS, Tallarida RJ, Ruggieri MR Sr: Interaction between muscarinic receptor subtype signal transduction pathways mediating bladder contraction. Am J Physiol Regul Integr Comp Physiol. 2002 Sep;283(3):R663-8. Pubmed
  4. Varoli L, Angeli P, Burnelli S, Marucci G, Recanatini M: Synthesis and antagonistic activity at muscarinic receptor subtypes of some 2-carbonyl derivatives of diphenidol. Bioorg Med Chem. 1999 Sep;7(9):1837-44. Pubmed
  5. Waelbroeck M, Camus J, Tastenoy M, Mutschler E, Strohmann C, Tacke R, Lambrecht G, Christophe J: Stereoselectivity of®- and (S)-hexahydro-difenidol binding to neuroblastoma M1, cardiac M2, pancreatic M3, and striatum M4 muscarinic receptors. Chirality. 1991;3(2):118-23. Pubmed

3. Muscarinic acetylcholine receptor M2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M2 P08172 Details

References:

  1. Pelat M, Lazartigues E, Tran MA, Gharib C, Montastruc JL, Montastruc P, Rascol O: Characterization of the central muscarinic cholinoceptors involved in the cholinergic pressor response in anesthetized dogs. Eur J Pharmacol. 1999 Aug 27;379(2-3):117-24. Pubmed
  2. Lazartigues E, Freslon JL, Tellioglu T, Brefel-Courbon C, Pelat M, Tran MA, Montastruc JL, Rascol O: Pressor and bradycardic effects of tacrine and other acetylcholinesterase inhibitors in the rat. Eur J Pharmacol. 1998 Nov 13;361(1):61-71. Pubmed
  3. Kovacs I, Yamamura HI, Waite SL, Varga EV, Roeske WR: Pharmacological comparison of the cloned human and rat M2 muscarinic receptor genes expressed in the murine fibroblast (B82) cell line. J Pharmacol Exp Ther. 1998 Feb;284(2):500-7. Pubmed
  4. Pavia J, Munoz M, Jimenez E, Martos F, Gonzalez-Correa JA, De la Cruz JP, Garcia V, Sanchez de la Cuesta F: Pharmacological characterization and distribution of muscarinic receptors in human placental syncytiotrophoblast brush-border and basal plasma membranes. Eur J Pharmacol. 1997 Feb 12;320(2-3):209-14. Pubmed
  5. Jovanovic A, Grbovic L, Tulic I: Endothelium-dependent relaxation in response to acetylcholine in the human uterine artery. Eur J Pharmacol. 1994 Apr 21;256(2):131-9. Pubmed
  6. Braverman AS, Tallarida RJ, Ruggieri MR Sr: Interaction between muscarinic receptor subtype signal transduction pathways mediating bladder contraction. Am J Physiol Regul Integr Comp Physiol. 2002 Sep;283(3):R663-8. Pubmed
  7. Varoli L, Angeli P, Burnelli S, Marucci G, Recanatini M: Synthesis and antagonistic activity at muscarinic receptor subtypes of some 2-carbonyl derivatives of diphenidol. Bioorg Med Chem. 1999 Sep;7(9):1837-44. Pubmed
  8. Waelbroeck M, Camus J, Tastenoy M, Mutschler E, Strohmann C, Tacke R, Lambrecht G, Christophe J: Stereoselectivity of®- and (S)-hexahydro-difenidol binding to neuroblastoma M1, cardiac M2, pancreatic M3, and striatum M4 muscarinic receptors. Chirality. 1991;3(2):118-23. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on April 14, 2014 16:09