Dimenhydrinate

Identification

Name
Dimenhydrinate
Accession Number
DB00985
Description

Dimenhydrinate, also known as Dramamine or Gravol, is an over-the-counter drug used to prevent nausea, vomiting, and dizziness caused by motion sickness. Dimenhydrinate is a combination drug composed of Diphenhydramine and 8-chlorotheophylline in a salt form, with 53%-55.5% of diphenhydramine, and not less than 44%-47% of 8-chlorotheophylline, calculated on the dried basis.

The antiemetic properties of dimenhydrinate are primarily thought to be produced by diphenhydramine's antagonism of H1 histamine receptors in the vestibular system 3 while the excitatory effects are thought to be produced by 8-chlorotheophylline's adenosine receptor blockade 4. The addition of 8-chlorotheophylline was initially intended to counteract the sedative effects of diphenhydramine.

When used in large doses, dimenhydrinate has been shown to cause a "high" characterized by hallucinations, excitement, incoordination, and disorientation 2.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 469.97
Monoisotopic: 469.1880675
Chemical Formula
C24H28ClN5O3
Synonyms
  • (O-benzhydryl(dimethylamino)ethanol) 8-chlorotheophyllinate
  • 8-chloro-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione - 2-(diphenylmethoxy)-N,N-dimethylethanamine (1:1)
  • Benzhydryl-β-dimethylaminoethylether 8-chlorotheophylline
  • Dimenhidrinato
  • Dimenhydrinate
  • Dimenhydrinatum
  • diphenhydramine 8-chlorotheophyllinate
  • diphenhydramine 8-chlorotheophylline
  • Diphenhydramine theoclate
  • N,N-dimethyl-2-diphenylmethoxyethylamine 8-chlorotheophyllinate
  • O-benzhydryldimethylaminoethanol 8-chlorotheophyllinate
  • β-dimethylaminoethyl benzhydryl ether 1,3-dimethyl-8-chloroxanthine

Pharmacology

Indication

Dimenhydrinate is indicated for the prevention and treatment of nausea, vomiting, or vertigo of motion sickness.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Dimenhydrinate is an antiemetics drug combination that contains diphenhydramine and theophylline. It is not effective in the treatment of nausea associated with cancer chemotherapy. Dimenhydrinate directly inhibits the stimulation of certain nerves in the brain and inner ear to suppress nausea, vomiting, dizziness, and vertigo. Diphenhydramine and dimenhydinate both reduce vestibular neuronal excitation due to angular or linear acceleration motions.

Mechanism of action

The mechanism by which some antihistamines exert their antiemetic, anti-motion sickness, and anti-vertigo effects is not precisely known but may be related to their central anticholinergic actions. They diminish vestibular stimulation and depress labyrinthine function. An action on the medullary chemoreceptive trigger zone may also be involved in the antiemetic effect. Dimenhydrinate is a competitive antagonist at the histamine H1 receptor, which is widely distributed in the human brain. Dimenhydrinate's anti-emetic effect is probably due to H1 antagonism in the vestibular system in the brain.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Humans
Absorption

Well absorbed after oral administration.

Volume of distribution
Not Available
Protein binding

98 to 99%.

Metabolism

Hepatic (cytochrome P-450 system).

Route of elimination
Not Available
Half-life

1 to 4 hours

Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

Symptoms of overdose include delerium, hallucinations, and excitment. Patients may be violent and confused.

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

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcebutololThe risk or severity of QTc prolongation can be increased when Dimenhydrinate is combined with Acebutolol.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Dimenhydrinate.
AcetophenazineThe risk or severity of adverse effects can be increased when Dimenhydrinate is combined with Acetophenazine.
AclidiniumDimenhydrinate may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.
AcrivastineThe risk or severity of QTc prolongation can be increased when Acrivastine is combined with Dimenhydrinate.
AdenosineThe risk or severity of QTc prolongation can be increased when Adenosine is combined with Dimenhydrinate.
AgomelatineThe risk or severity of adverse effects can be increased when Dimenhydrinate is combined with Agomelatine.
AjmalineThe risk or severity of QTc prolongation can be increased when Ajmaline is combined with Dimenhydrinate.
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Dimenhydrinate.
AlfuzosinThe risk or severity of QTc prolongation can be increased when Alfuzosin is combined with Dimenhydrinate.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Avoid alcohol.
  • Take with food.

Products

Active Moieties
NameKindUNIICASInChI Key
Diphenhydraminesalt8GTS82S83M58-73-1ZZVUWRFHKOJYTH-UHFFFAOYSA-N
8-chlorotheophyllinesaltGE2UA340FM85-18-7RYIGNEOBDRVTHA-UHFFFAOYSA-N
Product Images
International/Other Brands
Gravol (Church & Dwight) / Vertirosan (Astellas) / Vomex A (Astellas) / Xamamina (Adilna)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Dimenhydrinate Inj 10mgLiquidIntravenousSandoz Canada Incorporated1973-12-31Not applicableCanada
Dimenhydrinate Inj 10mg/mlLiquidIntravenousAstra Pharma Inc.1986-12-311999-07-29Canada
Dimenhydrinate Inj 50mg USPLiquidIntramuscular; IntravenousSandoz Canada Incorporated1973-12-31Not applicableCanada
Dimenhydrinate Injection 50mg/mlSolutionIntramuscular; IntravenousAstra Zeneca1986-12-312005-05-31Canada
Dimenhydrinate Injection USPSolutionIntramuscular; IntravenousTeligent Ou2016-01-28Not applicableCanada
Dimenhydrinate Injection USP 250mg/5ml (50mg/ml)SolutionIntramuscular; IntravenousTeligent Ou2008-06-26Not applicableCanada
Dimenhydrinate Injection USP With PreservativeSolutionIntramuscular; IntravenousTeligent Ou2016-01-28Not applicableCanada
Dimenhydrinate Injection, USPSolutionIntramuscular; IntravenousMylan Pharmaceuticals1994-12-31Not applicableCanada
Gravol ImSolutionIntramuscularChurch & Dwight Canada Corp1953-12-31Not applicableCanada
Gravol IV AmpoulesSolutionIntravenousChurch & Dwight Canada Corp1953-12-312008-07-30Canada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
DimenhydrinateInjection, solution50 mg/1mLIntramuscular; IntravenousFresenius Kabi USA, LLC2004-11-29Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Airmit AceTablet25 mg/1OralSato Pharmaceutical Co., Ltd.2005-03-11Not applicableUs
Anti-nauseantTabletOralPharmascience Inc2002-08-23Not applicableCanada
Anti-nauseantTabletOralApotex Corporation2013-07-02Not applicableCanada
Anti-nauseantTabletOralVita Health Products Inc2000-05-01Not applicableCanada
Anti-nauseantTabletOralPharmascience IncNot applicableNot applicableCanada
Anti-nauseantTabletOralTEVA Canada LimitedNot applicableNot applicableCanada
Anti-nauseant Liquid GelsCapsuleOralVita Health Products IncNot applicableNot applicableCanada
Anti-nauseant TabletTabletOralStanley Pharmaceuticals, A Division Of Vita Health Products Inc.1998-05-262008-08-07Canada
Apo Dimenhydrinate Tab 50mgTabletOralApotex Corporation1977-12-31Not applicableCanada
Children's Motion Sickness LiqSolutionOralTanta Pharmaceuticals Inc1996-12-31Not applicableCanada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Gravergol CapsulesDimenhydrinate (50 mg) + Caffeine (100 mg) + Ergotamine tartrate (1 mg)CapsuleOralCan Med Pharma Inc.1957-12-312011-12-07Canada

Categories

Drug Categories
Classification
Not classified

Chemical Identifiers

UNII
JB937PER5C
CAS number
523-87-5
InChI Key
NFLLKCVHYJRNRH-UHFFFAOYSA-N
InChI
InChI=1S/C17H21NO.C7H7ClN4O2/c1-18(2)13-14-19-17(15-9-5-3-6-10-15)16-11-7-4-8-12-16;1-11-4-3(9-6(8)10-4)5(13)12(2)7(11)14/h3-12,17H,13-14H2,1-2H3;1-2H3,(H,9,10)
IUPAC Name
8-chloro-1,3-dimethyl-2,3,6,9-tetrahydro-1H-purine-2,6-dione; [2-(diphenylmethoxy)ethyl]dimethylamine
SMILES
CN1C2=C(N=C(Cl)N2)C(=O)N(C)C1=O.CN(C)CCOC(C1=CC=CC=C1)C1=CC=CC=C1

References

Synthesis Reference

Cusic, J.W.; U.S. Patent 2,499,058; February 28,1950; assigned to G.D. Searle & Co. Cusic, J.W.; U.S. Patent 2,534,813; December 19,1950; assigned to G.D. Searle & Co.

General References
  1. Takeda N, Morita M, Hasegawa S, Horii A, Kubo T, Matsunaga T: Neuropharmacology of motion sickness and emesis. A review. Acta Otolaryngol Suppl. 1993;501:10-5. [PubMed:8447218]
  2. Halpert AG, Olmstead MC, Beninger RJ: Mechanisms and abuse liability of the anti-histamine dimenhydrinate. Neurosci Biobehav Rev. 2002 Jan;26(1):61-7. [PubMed:11835984]
  3. Jaju BP, Wang SC: Effects of diphenhydramine and dimenhydrinate on vestibular neuronal activity of cat: a search for the locus of their antimotion sickness action. J Pharmacol Exp Ther. 1971 Mar;176(3):718-24. [PubMed:4329456]
  4. Spealman RD: Psychomotor stimulant effects of methylxanthines in squirrel monkeys: relation to adenosine antagonism. Psychopharmacology (Berl). 1988;95(1):19-24. [PubMed:3133696]
Human Metabolome Database
HMDB0015120
KEGG Drug
D00520
PubChem Compound
441281
PubChem Substance
46504881
ChemSpider
10210
RxNav
3444
ChEBI
94848
ChEMBL
CHEMBL1200406
Therapeutic Targets Database
DAP000333
PharmGKB
PA449338
Drugs.com
Drugs.com Drug Page
Wikipedia
Dimenhydrinate
AHFS Codes
  • 56:22.08 — Antihistamines
  • 04:04.04 — Ethanolamine Derivatives
MSDS
Download (72 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedPreventionPost Operative Nausea and Vomiting (PONV)1
4CompletedTreatmentGastroenteritis1
4CompletedTreatmentNausea / Vertigo / Vomiting1
4CompletedTreatmentVertigo, Peripheral1
3RecruitingTreatmentVertigo, Peripheral1
2CompletedTreatmentPost Operative Nausea and Vomiting (PONV)1
1CompletedTreatmentHealthy Volunteers1
Not AvailableCompletedTreatmentNausea / Vomiting1

Pharmacoeconomics

Manufacturers
  • App pharmaceuticals llc
  • Baxter healthcare corp anesthesia and critical care
  • Watson laboratories inc
  • Wyeth ayerst laboratories
  • Alra laboratories inc
  • Heather drug co inc
  • Nexgen pharma inc
Packagers
  • APP Pharmaceuticals
  • C.O. Truxton Inc.
  • Consolidated Midland Corp.
  • Dispensing Solutions
  • Hospira Inc.
  • Ivax Pharmaceuticals
  • Major Pharmaceuticals
  • Martin Surgical Supply
  • Medisca Inc.
  • Nexgen Pharma Inc.
  • Pfizer Inc.
  • Pharmacia Inc.
  • Prescript Pharmaceuticals
  • Southwood Pharmaceuticals
Dosage Forms
FormRouteStrength
TabletOral25 mg/1
SolutionOral
Tablet50 MG
Injection, solutionIntramuscular; Intravenous50 mg/1mL
TabletOral50 mg/1
Tablet, film coatedOral50 mg/1
LiquidIntravenous
LiquidIntramuscular; Intravenous
SolutionIntramuscular; Intravenous
LiquidOral
TabletOral
Tablet, chewableOral50 mg/1
Tablet, chewableOral25 mg/1
CapsuleOral
Capsule, extended releaseOral
SolutionIntramuscular
Tablet, multilayerOral
SolutionIntravenous
CapsuleOral
Tablet, extended releaseOral
SuppositoryRectal
Tablet, chewableOral
SyrupOral
Tablet, coatedOral50 mg/1
Gum, chewingOral20 MG
Suppository150 MG
Tablet, sugar coatedOral50 MG
Suppository70 MG
Suppository40 MG
Tablet, orally disintegrating50 MG
Prices
Unit descriptionCostUnit
Dimenhydrinate 50 mg/ml vial5.7USD ml
Dimenhydrinate I.M. 50 mg/ml1.17USD ml
Meclizine 12.5 mg tablet0.62USD tablet
Dramamine less drowsy tablet0.42USD tablet
Dimenhydrinate I.V. 10 mg/ml0.32USD ml
Dramamine 50 mg tablet0.28USD tablet
Novamine 15% iv solution0.09USD ml
Dimenhydrinate 100% powder0.07USD g
Driminate 50 mg tablet0.05USD tablet
Dimenhydrinate 50 mg tablet0.03USD tablet
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)102.5-104Cusic, J.W.; U.S. Patent 2,499,058; February 28,1950; assigned to G.D. Searle & Co. Cusic, J.W.; U.S. Patent 2,534,813; December 19,1950; assigned to G.D. Searle & Co.
water solubility3000 mg/LMERCK INDEX (1996); approx.
logP-0.39Not Available
Predicted Properties
PropertyValueSource
Water Solubility9.86 mg/mLALOGPS
logP0.44ALOGPS
logP3.65ChemAxon
logS-1.3ALOGPS
pKa (Strongest Basic)8.87ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area12.47 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity79.93 m3·mol-1ChemAxon
Polarizability30.02 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9975
Blood Brain Barrier+0.8551
Caco-2 permeable+0.5198
P-glycoprotein substrateSubstrate0.7863
P-glycoprotein inhibitor INon-inhibitor0.6923
P-glycoprotein inhibitor IIInhibitor0.6502
Renal organic cation transporterNon-inhibitor0.6507
CYP450 2C9 substrateNon-substrate0.7536
CYP450 2D6 substrateNon-substrate0.8181
CYP450 3A4 substrateSubstrate0.7086
CYP450 1A2 substrateInhibitor0.5287
CYP450 2C9 inhibitorNon-inhibitor0.6308
CYP450 2D6 inhibitorNon-inhibitor0.8589
CYP450 2C19 inhibitorNon-inhibitor0.5817
CYP450 3A4 inhibitorNon-inhibitor0.9028
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5738
Ames testNon AMES toxic0.5629
CarcinogenicityNon-carcinogens0.7548
BiodegradationNot ready biodegradable0.8211
Rat acute toxicity2.4087 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5364
hERG inhibition (predictor II)Inhibitor0.5405
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

Kind
Protein
Organism
Humans
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 catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Halpert AG, Olmstead MC, Beninger RJ: Mechanisms and abuse liability of the anti-histamine dimenhydrinate. Neurosci Biobehav Rev. 2002 Jan;26(1):61-7. [PubMed:11835984]

Drug created on June 13, 2005 07:24 / Updated on August 02, 2020 22:18

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