DIPHENIDOL

US Previously Marketed

First approved in 1967

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 Search

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

Description
Sources: https://www.drugs.com/cons/diphenidol.html | https://www.ncbi.nlm.nih.gov/pubmed/26481789

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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Muscarinic acetylcholine receptor M1 169 Target ID: CHEMBL216 Sources: https://www.drugbank.ca/drugs/DB01231	Antagonist 2778	6.37 null [pKi]
Muscarinic acetylcholine receptor M2 121 Target ID: CHEMBL211 Sources: https://www.drugbank.ca/drugs/DB01231	Antagonist 2778	5.55 null [pKi]
Muscarinic acetylcholine receptor M3 159 Target ID: CHEMBL245 Sources: https://www.drugbank.ca/drugs/DB01231	Antagonist 2778	5.95 null [pKi]
Muscarinic acetylcholine receptor M4 86 Target ID: CHEMBL1821 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18395442	Antagonist 2778	6.04 null [pKi]
Muscarinic acetylcholine receptor M5 62 Target ID: CHEMBL2035 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18395442	Antagonist 2778	5.89 null [pKi]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Peripheral vertigo 3 Sources: https://www.drugs.com/cons/diphenidol.html	Primary		Approved 8429	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 1967

C_max

Value	Dose	Co-administered	Analyte	Population
157.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18506741/	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

Value	Dose	Co-administered	Analyte	Population
445.57 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18506741/	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.23 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18506741/	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

Dose	Population	Adverse events
15 mg/kg single, intravenous Highest studied dose Dose: 15 mg/kg Route: intravenous Route: single Dose: 15 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/1091418/	unhealthy, adult n = 18 Health Status: unhealthy Condition: tachyarrhythmias Age Group: adult Sex: unknown Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/1091418/	Disc. AE: Central nervous system disorder NOS... AEs leading to discontinuation/dose reduction: Central nervous system disorder NOS (14 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/1091418/

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/1091418/	unhealthy, adult n = 18 Health Status: unhealthy Condition: tachyarrhythmias Age Group: adult Sex: unknown Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/1091418/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OCT2 647	OCT2 355 UGT2B7 389

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
OCT2 648	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3971011/	yes [IC50 35 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
OCT2 355	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3971011/	no
UGT2B7 389	substrate 3367 Sources: http://www.latamjpharm.org/resumenes/35/9/LAJOP_35_9_2_6.pdf	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4638	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4638
ChemicalBook	CB8474607	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8474607
ZINC	ZINC000000968266	http://zinc15.docking.org/substances/ZINC000000968266
eMolecules	1986522	https://www.emolecules.com/cgi-bin/more?vid=1986522

PubMed

Title	Date	PubMed
Neuropharmacological mechanisms of emesis. I. Effects of antiemetic drugs on motion- and apomorphine-induced pica in rats.	1995 Nov	8786672
Simultaneous determination of enantiomers of structurally related anticholinergic analogs in human serum by liquid chromatography-electrospray ionization mass spectrometry with on-line sample cleanup.	2001 Oct 25	11678378
Synthesis and antagonistic activity at muscarinic receptor subtypes of some derivatives of diphenidol.	2003 Sep	13679157
Diphenidol has no actual broad antiemetic activity in dogs and ferrets.	2004 Nov	15528840
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	15967303
Determination of difenidol hydrochloride by capillary electrophoresis with electrochemiluminescence detection.	2006 Feb 2	16364700
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	17498727
A novel amperometric sensor for the detection of difenidol hydrochloride based on the modification of Ru(bpy)(3)(2+) on a glassy carbon electrode.	2007 Oct 15	19073084
Enzymatic preparation of cefaclor with immobilized penicillin acylase.	2008	18320464
Synthesis and pharmacological profile of a series of 1-substituted-2-carbonyl derivatives of Diphenidol: novel M4 muscarinic receptor antagonists.	2008 Mar	18336331
Effects of endolymphatic sac drainage with steroids for intractable Meniere's disease: a long-term follow-up and randomized controlled study.	2008 May	18520184
Diphenidol-related diamines as novel muscarinic M4 receptor antagonists.	2008 May 1	18395442
Ultra-fast chromatographic micro-assay for quantification of diphenidol in plasma: application in an oral multi-dose switchability trial.	2008 Oct	18506741
[Clinical analysis on the cervical vertigo after operation of middle ear].	2009 May	19670624
(2-Methyl-phen-yl)(phen-yl)methanol.	2010 Jul 31	21588424
Diphenidol inhibited sodium currents and produced spinal anesthesia.	2010 Jun	20176039
Neuropharmacology of vestibular system disorders.	2010 Mar	20808544
Generation of gold nanostructures at the surface of platinum electrode by electrodeposition for ECL detection for CE.	2010 Mar	20309916
Evaluation of phenoxybenzamine in the CFA model of pain following gene expression studies and connectivity mapping.	2010 Sep 16	20846436
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.	2011 Jul 14	21599003

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 Use Guide

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 GMT 2023` Edited by `admin` on `Fri Dec 15 15:14:18 GMT 2023`
Record UNII	NQO8R319LY
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DIPHENIDOL

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

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