Identification

Name
Dimenhydrinate
Accession Number
DB00985  (APRD00924)
Type
Small Molecule
Groups
Approved
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].

Structure
Thumb
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
  • 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
Active Moieties
NameKindUNIICASInChI Key
Diphenhydraminesalt8GTS82S83M58-73-1ZZVUWRFHKOJYTH-UHFFFAOYSA-N
8-chlorotheophyllinesaltGE2UA340FM85-18-7RYIGNEOBDRVTHA-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Dimenhydrinate Inj 10mgLiquid10 mgIntravenousSandoz Canada Incorporated1973-12-31Not applicableCanada
Dimenhydrinate Inj 10mg/mlLiquid10 mgIntravenousAstra Pharma Inc.1986-12-311999-07-29Canada
Dimenhydrinate Inj 50mg USPLiquid50 mgIntramuscular; IntravenousSandoz Canada Incorporated1973-12-31Not applicableCanada
Dimenhydrinate Injection 50mg/mlSolution50 mgIntramuscular; IntravenousAstra Zeneca1986-12-312005-05-31Canada
Dimenhydrinate Injection USPSolution50 mgIntramuscular; IntravenousTeligent Ou2016-01-28Not applicableCanada
Dimenhydrinate Injection USP 250mg/5ml (50mg/ml)Solution50 mgIntramuscular; IntravenousAlveda Pharmaceuticals Inc2008-06-26Not applicableCanada
Dimenhydrinate Injection USP With PreservativeSolution50 mgIntramuscular; IntravenousTeligent Ou2016-01-28Not applicableCanada
Dimenhydrinate Injection, USPSolution50 mgIntramuscular; IntravenousMylan Pharmaceuticals1994-12-31Not applicableCanada
Gravol ImSolution50 mgIntramuscularChurch & Dwight Company, Inc.1953-12-31Not applicableCanada
Gravol IV AmpoulesSolution10 mgIntravenousChurch & Dwight Company, Inc.1953-12-312008-07-30Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DimenhydrinateInjection, solution50 mg/1mLIntramuscular; IntravenousFresenius Kabi USA, LLC2004-11-29Not applicableUs
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Airmit AceTablet25 mg/1OralSato Pharmaceutical2005-03-11Not applicableUs
Anti-nauseantTablet50 mgOralPharmascience IncNot applicableNot applicableCanada
Anti-nauseantTablet50 mgOralPharmascience Inc2002-08-23Not applicableCanada
Anti-nauseantTablet50 mgOralApotex Corporation2013-07-02Not applicableCanada
Anti-nauseantTablet50 mgOralVita Health Products Inc2000-05-01Not applicableCanada
Anti-nauseantTablet50 mgOralTevaNot applicableNot applicableCanada
Anti-nauseant TabletTablet50 mgOralStanley Pharmaceuticals, A Division Of Vita Health Products Inc.1998-05-262008-08-07Canada
Apo Dimenhydrinate Tab 50mgTablet50 mgOralApotex Corporation1977-12-31Not applicableCanada
Children's Motion Sickness LiqSolution15 mgOralTanta Pharmaceuticals Inc1996-12-31Not applicableCanada
Children's Motion Sickness LiquidSolution15 mgOralAra Avanti Rx Analytics IncNot applicableNot applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Gravergol CapsulesDimenhydrinate (50 mg) + Caffeine (100 mg) + Ergotamine tartrate (1 mg)CapsuleOralCan Med Pharma Inc.1957-12-312011-12-07Canada
International/Other Brands
Gravol (Church & Dwight) / Vertirosan (Astellas) / Vomex A (Astellas) / Xamamina (Adilna)
Categories
UNII
JB937PER5C
CAS number
523-87-5
Weight
Average: 469.964
Monoisotopic: 469.188067494
Chemical Formula
C24H28ClN5O3
InChI Key
DKHVTDUUNTVKOW-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,9,10,13)
IUPAC Name
8-chloro-1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-7-ide; [2-(diphenylmethoxy)ethyl]dimethylazanium
SMILES
CN1C2=C([N-]C(Cl)=N2)C(=O)N(C)C1=O.C[NH+](C)CCOC(C1=CC=CC=C1)C1=CC=CC=C1

Pharmacology

Indication

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

Associated Conditions
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
Human
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
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
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative and stimulatory activities of Dimenhydrinate.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative and stimulatory activities of Dimenhydrinate.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative and stimulatory activities of Dimenhydrinate.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative and stimulatory activities of Dimenhydrinate.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Dimenhydrinate is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Dimenhydrinate is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Dimenhydrinate is combined with 7-Nitroindazole.
AbexinostatThe risk or severity of QTc prolongation can be increased when Dimenhydrinate is combined with Abexinostat.
AcebutololThe risk or severity of QTc prolongation can be increased when Dimenhydrinate is combined with Acebutolol.
AcepromazineThe risk or severity of adverse effects can be increased when Dimenhydrinate is combined with Acepromazine.
Food Interactions
  • Avoid alcohol.
  • Take with food.

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]
External Links
Human Metabolome Database
HMDB0015120
KEGG Drug
D00520
PubChem Compound
441281
PubChem Substance
46504881
ChemSpider
10468539
ChEBI
4604
ChEMBL
CHEMBL1200406
Therapeutic Targets Database
DAP000333
PharmGKB
PA449338
Drugs.com
Drugs.com Drug Page
Wikipedia
Dimenhydrinate
AHFS Codes
  • 56:22.08 — Antihistamines
MSDS
Download (72 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentPost-Operative Nausea and Vomiting (PONV)1
2RecruitingTreatmentUrinary Bladder, Overactive1
3RecruitingTreatmentVertigo, Peripheral1
4CompletedPreventionPost-Operative Nausea and Vomiting (PONV)1
4CompletedTreatmentGastroenteritis1
4CompletedTreatmentNausea / Vertigo / Vomiting1
4CompletedTreatmentVertigo, Peripheral1
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
SolutionOral15 mg
Injection, solutionIntramuscular; Intravenous50 mg/1mL
TabletOral50 mg/1
Tablet, film coatedOral50 mg/1
LiquidIntravenous10 mg
LiquidIntramuscular; Intravenous50 mg
SolutionIntramuscular; Intravenous50 mg
LiquidOral15 mg
TabletOral50 mg
TabletOral50.0 mg
Tablet, chewableOral50 mg/1
Tablet, chewableOral25 mg/1
CapsuleOral
Capsule, extended releaseOral75 mg
SuppositoryRectal100 mg
TabletOral15 mg
SolutionIntramuscular50 mg
Tablet, multilayerOral100 mg
SolutionIntravenous10 mg
SuppositoryRectal25 mg
SyrupOral15 mg
Tablet, chewableOral15 mg
Tablet, extended releaseOral75 mg
Tablet, chewableOral50 mg
TabletOral25 mg
CapsuleOral50 mg
Tablet, coatedOral50 mg/1
SyrupOral3 mg
SuppositoryRectal50 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 Solubility0.00125 mg/mLALOGPS
logP2.67ALOGPS
logP3.65ChemAxon
logS-5.6ALOGPS
pKa (Strongest Basic)8.87ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area13.67 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity90.94 m3·mol-1ChemAxon
Polarizability30.28 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
SpectrumSpectrum TypeSplash Key
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
Xanthines / 6-oxopurines / Alkaloids and derivatives / Benzylethers / Pyrimidones / Aryl chlorides / Vinylogous amides / Heteroaromatic compounds / Imidazoles / Ureas
show 9 more
Substituents
Diphenylmethane / Xanthine / 6-oxopurine / Purinone / Purine / Benzylether / Alkaloid or derivatives / Imidazopyrimidine / Pyrimidone / Aryl chloride
show 26 more
Molecular Framework
Not Available
External Descriptors
organic salt (CHEBI:4604)

Targets

Kind
Protein
Organism
Human
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 December 10, 2018 13:39