U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C21H27NO
Molecular Weight 309.4452
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DIPHENIDOL

SMILES

OC(CCCN1CCCCC1)(C2=CC=CC=C2)C3=CC=CC=C3

InChI

InChIKey=OGAKLTJNUQRZJU-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Molecular Formula C21H27NO
Molecular Weight 309.4452
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Diphenidol, a nonphenothiazinic antiemetic agent used primarily in patients with Meniere disease and labyrinthopathies to treat vomiting and vertigo, is considered to be a relatively safe drug. Since it was first approved in the United States in 1967, this drug has been widely used in Latin America and Asia and has contributed to sporadic suicidal and accidental poisonings in mainland China and Taiwan. 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. Diphenidol is used to relieve or prevent nausea, vomiting, and dizziness caused by certain medical problems.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
VONTROL

Approved Use

INDICATIONS VERTIGO—‘Vontrol’ is indicated in peripheral (labyrinthine) vertigo and associated nausea and vomiting, as seen in such conditions as: Meniere’s disease, middle- and inner-ear surgery (labyrinthitis). NAUSEA AND VOMITING—‘Vontrol’ is indicated in the control of nausea and vomiting, as seen in such conditions as: postoperative states, malignant neoplasms and labyrinthine disturbances.

Launch Date

-8.6572802E10
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
157.4 ng/mL
25 mg 2 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIPHENIDOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
445.57 ng × h/mL
25 mg 2 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIPHENIDOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3.23 h
25 mg 2 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIPHENIDOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
Doses

Doses

DosePopulationAdverse events​
15 mg/kg single, intravenous
Highest studied dose
Dose: 15 mg/kg
Route: intravenous
Route: single
Dose: 15 mg/kg
Sources:
unhealthy, adult
n = 18
Health Status: unhealthy
Condition: tachyarrhythmias
Age Group: adult
Sex: unknown
Population Size: 18
Sources:
Disc. AE: Central nervous system disorder NOS...
AEs leading to
discontinuation/dose reduction:
Central nervous system disorder NOS (14 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Central nervous system disorder NOS 14 patients
Disc. AE
15 mg/kg single, intravenous
Highest studied dose
Dose: 15 mg/kg
Route: intravenous
Route: single
Dose: 15 mg/kg
Sources:
unhealthy, adult
n = 18
Health Status: unhealthy
Condition: tachyarrhythmias
Age Group: adult
Sex: unknown
Population Size: 18
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer



Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [IC50 35 uM]
Drug as victim
PubMed

PubMed

TitleDatePubMed
Neuropharmacological mechanisms of emesis. I. Effects of antiemetic drugs on motion- and apomorphine-induced pica in rats.
1995 Nov
Synthesis and antagonistic activity at muscarinic receptor subtypes of some derivatives of diphenidol.
2003 Sep
Diphenidol has no actual broad antiemetic activity in dogs and ferrets.
2004 Nov
Development of an HPLC method for determination of diphenidol in plasma and its application in an oral multi-dose bioequivalence study in a healthy female Mexican population.
2005 Jul 15
Determination of difenidol hydrochloride by capillary electrophoresis with electrochemiluminescence detection.
2006 Feb 2
Capillary electrophoresis with end-column electrochemiluminescence for the analysis of chloroquine phosphate and the study on its interaction with human serum albumin.
2007 Jun 22
Enzymatic preparation of cefaclor with immobilized penicillin acylase.
2008
Synthesis and pharmacological profile of a series of 1-substituted-2-carbonyl derivatives of Diphenidol: novel M4 muscarinic receptor antagonists.
2008 Mar
Ultra-fast chromatographic micro-assay for quantification of diphenidol in plasma: application in an oral multi-dose switchability trial.
2008 Oct
(2-Methyl-phen-yl)(phen-yl)methanol.
2010 Jul 31
Generation of gold nanostructures at the surface of platinum electrode by electrodeposition for ECL detection for CE.
2010 Mar
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.
2011 Jul 14
Patents

Patents

Sample Use Guides

In Vivo Use Guide
For oral dosage form (tablets): Adults: 25 to 50 milligrams (mg) every four hours as needed.
Route of Administration: Oral
In vitro binding assays demonstrated that difenidol at micromolar concentrations bound to the α(1A)-, α(1B)- and α(1D)-adrenoceptor subtypes. Difenidol inhibited the phenylephrine-induced increase in [Ca(2+)](i) in Chinese hamster ovary cells expressing human α(1A)-, α(1B)- or α(1D)-adrenoceptor subtypes with similar IC(50) values in the low micromolar range.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:14:18 UTC 2023
Edited
by admin
on Fri Dec 15 15:14:18 UTC 2023
Record UNII
NQO8R319LY
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DIPHENIDOL
HSDB   MI   USAN   VANDF  
USAN  
Official Name English
α,α-Diphenyl-1-piperidinebutanol
Systematic Name English
DIPHENIDOL [MI]
Common Name English
DIPHENIDOL [VANDF]
Common Name English
DIPHENIDOL [USAN]
Common Name English
DIPHENIDOL [HSDB]
Common Name English
SK&F 478
Code English
DIFENIDOL
INN   WHO-DD  
INN  
Official Name English
1-PIPERIDINEBUTANOL, .ALPHA.,.ALPHA.-DIPHENYL-
Systematic Name English
SK&F-478
Code English
Difenidol [WHO-DD]
Common Name English
difenidol [INN]
Common Name English
Classification Tree Code System Code
NDF-RT N0000009034
Created by admin on Fri Dec 15 15:14:18 UTC 2023 , Edited by admin on Fri Dec 15 15:14:18 UTC 2023
NDF-RT N0000009034
Created by admin on Fri Dec 15 15:14:18 UTC 2023 , Edited by admin on Fri Dec 15 15:14:18 UTC 2023
NDF-RT N0000178372
Created by admin on Fri Dec 15 15:14:18 UTC 2023 , Edited by admin on Fri Dec 15 15:14:18 UTC 2023
NCI_THESAURUS C267
Created by admin on Fri Dec 15 15:14:18 UTC 2023 , Edited by admin on Fri Dec 15 15:14:18 UTC 2023
Code System Code Type Description
MERCK INDEX
m4611
Created by admin on Fri Dec 15 15:14:18 UTC 2023 , Edited by admin on Fri Dec 15 15:14:18 UTC 2023
PRIMARY Merck Index
CHEBI
4638
Created by admin on Fri Dec 15 15:14:18 UTC 2023 , Edited by admin on Fri Dec 15 15:14:18 UTC 2023
PRIMARY
CAS
972-02-1
Created by admin on Fri Dec 15 15:14:18 UTC 2023 , Edited by admin on Fri Dec 15 15:14:18 UTC 2023
PRIMARY
FDA UNII
NQO8R319LY
Created by admin on Fri Dec 15 15:14:18 UTC 2023 , Edited by admin on Fri Dec 15 15:14:18 UTC 2023
PRIMARY
NCI_THESAURUS
C65421
Created by admin on Fri Dec 15 15:14:18 UTC 2023 , Edited by admin on Fri Dec 15 15:14:18 UTC 2023
PRIMARY
ECHA (EC/EINECS)
213-540-9
Created by admin on Fri Dec 15 15:14:18 UTC 2023 , Edited by admin on Fri Dec 15 15:14:18 UTC 2023
PRIMARY
EVMPD
SUB07121MIG
Created by admin on Fri Dec 15 15:14:18 UTC 2023 , Edited by admin on Fri Dec 15 15:14:18 UTC 2023
PRIMARY
ChEMBL
CHEMBL936
Created by admin on Fri Dec 15 15:14:18 UTC 2023 , Edited by admin on Fri Dec 15 15:14:18 UTC 2023
PRIMARY
RXCUI
23370
Created by admin on Fri Dec 15 15:14:18 UTC 2023 , Edited by admin on Fri Dec 15 15:14:18 UTC 2023
PRIMARY RxNorm
SMS_ID
100000083173
Created by admin on Fri Dec 15 15:14:18 UTC 2023 , Edited by admin on Fri Dec 15 15:14:18 UTC 2023
PRIMARY
PUBCHEM
3055
Created by admin on Fri Dec 15 15:14:18 UTC 2023 , Edited by admin on Fri Dec 15 15:14:18 UTC 2023
PRIMARY
INN
1433
Created by admin on Fri Dec 15 15:14:18 UTC 2023 , Edited by admin on Fri Dec 15 15:14:18 UTC 2023
PRIMARY
DRUG CENTRAL
313
Created by admin on Fri Dec 15 15:14:18 UTC 2023 , Edited by admin on Fri Dec 15 15:14:18 UTC 2023
PRIMARY
DRUG BANK
DB01231
Created by admin on Fri Dec 15 15:14:18 UTC 2023 , Edited by admin on Fri Dec 15 15:14:18 UTC 2023
PRIMARY
EPA CompTox
DTXSID3022950
Created by admin on Fri Dec 15 15:14:18 UTC 2023 , Edited by admin on Fri Dec 15 15:14:18 UTC 2023
PRIMARY
MESH
C004858
Created by admin on Fri Dec 15 15:14:18 UTC 2023 , Edited by admin on Fri Dec 15 15:14:18 UTC 2023
PRIMARY
HSDB
3316
Created by admin on Fri Dec 15 15:14:18 UTC 2023 , Edited by admin on Fri Dec 15 15:14:18 UTC 2023
PRIMARY
WIKIPEDIA
DIPHENIDOL
Created by admin on Fri Dec 15 15:14:18 UTC 2023 , Edited by admin on Fri Dec 15 15:14:18 UTC 2023
PRIMARY
IUPHAR
7163
Created by admin on Fri Dec 15 15:14:18 UTC 2023 , Edited by admin on Fri Dec 15 15:14:18 UTC 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
Related Record Type Details
ACTIVE MOIETY