Identification

Name
Diphenidol
Accession Number
DB01231  (APRD00929)
Type
Small Molecule
Groups
Approved, Investigational, Withdrawn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
  • alpha,alpha-Diphenyl-1-piperidinebutanol
  • Difenidol
  • Difenidolo
  • Difenidolum
  • Diphenidol
  • Diphenyl(3-(1-piperidyl)propyl)carbinol
Product Ingredients
IngredientUNIICASInChI Key
Diphenidol HydrochlorideDG355XWQ4T3254-89-5AVZIYZHXZAYGJS-UHFFFAOYSA-N
International/Other Brands
Satanolon (Tatsumi Kagaku) / Verterge / Vontrol (Sanfer) / Yesdol
Categories
UNII
NQO8R319LY
CAS number
972-02-1
Weight
Average: 309.4452
Monoisotopic: 309.209264491
Chemical Formula
C21H27NO
InChI Key
OGAKLTJNUQRZJU-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

Pharmacology

Indication

For 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.

Structured Indications
Not Available
Pharmacodynamics

Diphenidol 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 action

The 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.

TargetActionsOrganism
AMuscarinic acetylcholine receptor M2
antagonist
Human
AMuscarinic acetylcholine receptor M1
antagonist
Human
AMuscarinic acetylcholine receptor M3
antagonist
Human
Absorption

Well absorbed from gastrointestinal tract following oral administration.

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

4 hours

Clearance
Not Available
Toxicity

Symptoms of overdose include drowsiness (severe); shortness of breath or troubled breathing; unusual tiredness or weakness (severe).

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not 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 References
  1. Link [Link]
External Links
Human Metabolome Database
HMDB15361
KEGG Drug
D03858
KEGG Compound
C06961
PubChem Compound
3055
PubChem Substance
46506486
ChemSpider
2947
ChEBI
4638
ChEMBL
CHEMBL936
Therapeutic Targets Database
DAP001133
PharmGKB
PA164746037
Drugs.com
Drugs.com Drug Page
FDA label
Download (374 KB)
MSDS
Download (73.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentMenière's Disease / Vertigo1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Professional Co.
Dosage forms
Not Available
Prices
Unit descriptionCostUnit
Diphenidol hcl powder32.4USD g
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)212-214Miescher, 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 Solubility0.00587 mg/mLALOGPS
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 Area23.47 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity96.92 m3·mol-1ChemAxon
Polarizability36.66 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9296
Blood Brain Barrier+0.9606
Caco-2 permeable+0.6951
P-glycoprotein substrateSubstrate0.7254
P-glycoprotein inhibitor IInhibitor0.5603
P-glycoprotein inhibitor IINon-inhibitor0.7523
Renal organic cation transporterInhibitor0.7647
CYP450 2C9 substrateNon-substrate0.8378
CYP450 2D6 substrateNon-substrate0.7102
CYP450 3A4 substrateNon-substrate0.5631
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9255
CYP450 2D6 inhibitorInhibitor0.9373
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.7862
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9362
Ames testNon AMES toxic0.8763
CarcinogenicityNon-carcinogens0.924
BiodegradationNot ready biodegradable0.9177
Rat acute toxicity2.6101 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.6086
hERG inhibition (predictor II)Inhibitor0.6009
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
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
Phenylbutylamines / Aralkylamines / Piperidines / Tertiary alcohols / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives / Aromatic alcohols
Substituents
Diphenylmethane / Phenylbutylamine / Aralkylamine / Piperidine / Tertiary alcohol / Tertiary amine / Tertiary aliphatic amine / Organoheterocyclic compound / Azacycle / Aromatic alcohol
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
piperidines, tertiary alcohol, benzenes (CHEBI:4638)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
G-protein coupled acetylcholine receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM2
Uniprot ID
P08172
Uniprot Name
Muscarinic acetylcholine receptor M2
Molecular Weight
51714.605 Da
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:10497897]
  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:9851542]
  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:9454790]
  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:9059856]
  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:8050463]
  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:12185001]
  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:10530931]
  8. Waelbroeck M, Camus J, Tastenoy M, Mutschler E, Strohmann C, Tacke R, Lambrecht G, Christophe J: Stereoselectivity of (R)- and (S)-hexahydro-difenidol binding to neuroblastoma M1, cardiac M2, pancreatic M3, and striatum M4 muscarinic receptors. Chirality. 1991;3(2):118-23. [PubMed:1863523]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 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. Waelbroeck M, Camus J, Tastenoy M, Mutschler E, Strohmann C, Tacke R, Lambrecht G, Christophe J: Stereoselectivity of (R)- and (S)-hexahydro-difenidol binding to neuroblastoma M1, cardiac M2, pancreatic M3, and striatum M4 muscarinic receptors. Chirality. 1991;3(2):118-23. [PubMed:1863523]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM3
Uniprot ID
P20309
Uniprot Name
Muscarinic acetylcholine receptor M3
Molecular Weight
66127.445 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. 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:12185001]
  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:10530931]
  5. Waelbroeck M, Camus J, Tastenoy M, Mutschler E, Strohmann C, Tacke R, Lambrecht G, Christophe J: Stereoselectivity of (R)- and (S)-hexahydro-difenidol binding to neuroblastoma M1, cardiac M2, pancreatic M3, and striatum M4 muscarinic receptors. Chirality. 1991;3(2):118-23. [PubMed:1863523]

Drug created on June 13, 2005 07:24 / Updated on November 09, 2017 02:57