- Accession Number
- DB00985 (APRD00924)
- Small Molecule
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  while the excitatory effects are thought to be produced by 8-chlorotheophylline's adenosine receptor blockade . 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 .
- (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
- 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
Name Kind UNII CAS InChI Key Diphenhydramine salt 8GTS82S83M 58-73-1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 8-chlorotheophylline salt GE2UA340FM 85-18-7 RYIGNEOBDRVTHA-UHFFFAOYSA-N
- Product Images
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Dimenhydrinate Inj 10mg Liquid 10 mg Intravenous Sandoz Canada Incorporated 1973-12-31 Not applicable Dimenhydrinate Inj 10mg/ml Liquid 10 mg Intravenous Astra Pharma Inc. 1986-12-31 1999-07-29 Dimenhydrinate Inj 50mg USP Liquid 50 mg Intramuscular; Intravenous Sandoz Canada Incorporated 1973-12-31 Not applicable Dimenhydrinate Injection 50mg/ml Solution 50 mg Intramuscular; Intravenous Astra Zeneca 1986-12-31 2005-05-31 Dimenhydrinate Injection USP Solution 50 mg Intramuscular; Intravenous Teligent Ou 2016-01-28 Not applicable Dimenhydrinate Injection USP 250mg/5ml (50mg/ml) Solution 50 mg Intramuscular; Intravenous Alveda Pharmaceuticals Inc 2008-06-26 Not applicable Dimenhydrinate Injection USP With Preservative Solution 50 mg Intramuscular; Intravenous Teligent Ou 2016-01-28 Not applicable Dimenhydrinate Injection, USP Solution 50 mg Intramuscular; Intravenous Mylan Pharmaceuticals 1994-12-31 Not applicable Gravol Im Solution 50 mg Intramuscular Church & Dwight Company, Inc. 1953-12-31 Not applicable Gravol IV Ampoules Solution 10 mg Intravenous Church & Dwight Company, Inc. 1953-12-31 2008-07-30
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Dimenhydrinate Injection, solution 50 mg/1mL Intramuscular; Intravenous APP Pharmaceuticals, Inc. 2004-11-29 Not applicable
- Over the Counter Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Airmit Ace Tablet 25 mg/1 Oral Sato Pharmaceutical 2005-03-11 Not applicable Anti-nauseant Tablet 50 mg Oral Apotex Corporation 2013-07-02 Not applicable Anti-nauseant Tablet 50 mg Oral Teva Not applicable Not applicable Anti-nauseant Tablet 50 mg Oral Pharmascience Inc 2002-08-23 Not applicable Anti-nauseant Tablet 50 mg Oral Pharmascience Inc Not applicable Not applicable Anti-nauseant Tablet 50 mg Oral Vita Health Products Inc 2000-05-01 Not applicable Anti-nauseant Tablet Tablet 50 mg Oral Stanley Pharmaceuticals, A Division Of Vita Health Products Inc. 1998-05-26 2008-08-07 Apo Dimenhydrinate Tab 50mg Tablet 50 mg Oral Apotex Corporation 1977-12-31 Not applicable Children's Motion Sickness Liq Solution 15 mg Oral Tanta Pharmaceuticals Inc 1996-12-31 Not applicable Children's Motion Sickness Liquid Solution 15 mg Oral Ara Avanti Rx Analytics Inc Not applicable Not applicable
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Gravergol Capsules Dimenhydrinate (50 mg) + Caffeine (100 mg) + Ergotamine tartrate (1 mg) Capsule Oral Can Med Pharma Inc. 1957-12-31 2011-12-07
- International/Other Brands
- Gravol (Church & Dwight) / Vertirosan (Astellas) / Vomex A (Astellas) / Xamamina (Adilna)
- Autonomic Agents
- Benzene Derivatives
- Benzhydryl Compounds
- Central Nervous System Agents
- Central Nervous System Depressants
- Gastrointestinal Agents
- Histamine Agents
- Histamine Antagonists
- Histamine H1 Antagonists
- Moderate Risk QTc-Prolonging Agents
- Neurotransmitter Agents
- Peripheral Nervous System Agents
- Pharmaceutical Preparations
- QTc Prolonging Agents
- CAS number
- Average: 469.964
- Chemical Formula
- InChI Key
- IUPAC Name
- 8-chloro-1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-7-ide; [2-(diphenylmethoxy)ethyl]dimethylazanium
Dimenhydrinate is indicated for the prevention and treatment of nausea, vomiting, or vertigo of motion sickness.
- Associated Conditions
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.
Target Actions Organism AHistamine H1 receptorantagonist Human
Well absorbed after oral administration.
- Volume of distribution
- Not Available
- Protein binding
98 to 99%.
Hepatic (cytochrome P-450 system).
- Route of elimination
- Not Available
- Half life
1 to 4 hours
- Not Available
Symptoms of overdose include delerium, hallucinations, and excitment. Patients may be violent and confused.
- Affected organisms
- Humans and other mammals
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
- Drug Interactions
Drug Interaction 2,5-Dimethoxy-4-ethylamphetamine 2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative and stimulatory activities of Dimenhydrinate. 2,5-Dimethoxy-4-ethylthioamphetamine 2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative and stimulatory activities of Dimenhydrinate. 3,4-Methylenedioxyamphetamine 3,4-Methylenedioxyamphetamine may decrease the sedative and stimulatory activities of Dimenhydrinate. 4-Bromo-2,5-dimethoxyamphetamine 4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative and stimulatory activities of Dimenhydrinate. 4-Methoxyamphetamine The risk or severity of adverse effects can be increased when Dimenhydrinate is combined with 4-Methoxyamphetamine. 5-methoxy-N,N-dimethyltryptamine The risk or severity of adverse effects can be increased when Dimenhydrinate is combined with 5-methoxy-N,N-dimethyltryptamine. 7-Nitroindazole The risk or severity of adverse effects can be increased when Dimenhydrinate is combined with 7-Nitroindazole. 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline The risk or severity of adverse effects can be increased when Dimenhydrinate is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline. Abexinostat The risk or severity of QTc prolongation can be increased when Dimenhydrinate is combined with Abexinostat. Acebutolol The risk or severity of QTc prolongation can be increased when Dimenhydrinate is combined with Acebutolol.
- Food Interactions
- Avoid alcohol.
- Take with food.
- 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
- 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]
- 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]
- 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]
- 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
- AHFS Codes
- 56:22.08 — Antihistamines
- Download (72 KB)
- Clinical Trials
Phase Status Purpose Conditions Count 2 Completed Treatment Post-Operative Nausea and Vomiting (PONV) 1 2 Recruiting Treatment Urinary Bladder, Overactive 1 3 Recruiting Treatment Vertigo, Peripheral 1 4 Completed Prevention Post-Operative Nausea and Vomiting (PONV) 1 4 Completed Treatment Gastroenteritis 1 4 Completed Treatment Nausea / Vertigo / Vomiting 1 4 Completed Treatment Vertigo, Peripheral 1 Not Available Completed Treatment Nausea / Vomiting 1
- 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
- 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
Form Route Strength Tablet Oral 25 mg/1 Solution Oral 15 mg Injection, solution Intramuscular; Intravenous 50 mg/1mL Tablet Oral 50 mg/1 Tablet, film coated Oral 50 mg/1 Liquid Intravenous 10 mg Liquid Intramuscular; Intravenous 50 mg Solution Intramuscular; Intravenous 50 mg Liquid Oral 15 mg Tablet Oral 50 mg Tablet Oral 50.0 mg Tablet, chewable Oral 50 mg/1 Tablet, chewable Oral 25 mg/1 Capsule Oral Capsule, extended release Oral 75 mg Suppository Rectal 100 mg Tablet Oral 15 mg Solution Intramuscular 50 mg Tablet, multilayer Oral 100 mg Solution Intravenous 10 mg Suppository Rectal 25 mg Syrup Oral 15 mg Tablet, chewable Oral 15 mg Tablet, extended release Oral 75 mg Tablet, chewable Oral 50 mg Tablet Oral 25 mg Capsule Oral 50 mg Tablet, coated Oral 50 mg/1 Syrup Oral 3 mg Suppository Rectal 50 mg
Unit description Cost Unit Dimenhydrinate 50 mg/ml vial 5.7USD ml Dimenhydrinate I.M. 50 mg/ml 1.17USD ml Meclizine 12.5 mg tablet 0.62USD tablet Dramamine less drowsy tablet 0.42USD tablet Dimenhydrinate I.V. 10 mg/ml 0.32USD ml Dramamine 50 mg tablet 0.28USD tablet Novamine 15% iv solution 0.09USD ml Dimenhydrinate 100% powder 0.07USD g Driminate 50 mg tablet 0.05USD tablet Dimenhydrinate 50 mg tablet 0.03USD tabletDrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
- Not Available
- Experimental Properties
Property Value Source melting point (°C) 102.5-104 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. water solubility 3000 mg/L MERCK INDEX (1996); approx. logP -0.39 Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00125 mg/mL ALOGPS logP 2.67 ALOGPS logP 3.65 ChemAxon logS -5.6 ALOGPS pKa (Strongest Basic) 8.87 ChemAxon Physiological Charge 1 ChemAxon Hydrogen Acceptor Count 1 ChemAxon Hydrogen Donor Count 1 ChemAxon Polar Surface Area 13.67 Å2 ChemAxon Rotatable Bond Count 6 ChemAxon Refractivity 90.94 m3·mol-1 ChemAxon Polarizability 30.28 Å3 ChemAxon Number of Rings 4 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule Yes ChemAxon MDDR-like Rule Yes ChemAxon
- Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 0.9975 Blood Brain Barrier + 0.8551 Caco-2 permeable + 0.5198 P-glycoprotein substrate Substrate 0.7863 P-glycoprotein inhibitor I Non-inhibitor 0.6923 P-glycoprotein inhibitor II Inhibitor 0.6502 Renal organic cation transporter Non-inhibitor 0.6507 CYP450 2C9 substrate Non-substrate 0.7536 CYP450 2D6 substrate Non-substrate 0.8181 CYP450 3A4 substrate Substrate 0.7086 CYP450 1A2 substrate Inhibitor 0.5287 CYP450 2C9 inhibitor Non-inhibitor 0.6308 CYP450 2D6 inhibitor Non-inhibitor 0.8589 CYP450 2C19 inhibitor Non-inhibitor 0.5817 CYP450 3A4 inhibitor Non-inhibitor 0.9028 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5738 Ames test Non AMES toxic 0.5629 Carcinogenicity Non-carcinogens 0.7548 Biodegradation Not ready biodegradable 0.8211 Rat acute toxicity 2.4087 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.5364 hERG inhibition (predictor II) Inhibitor 0.5405
- Mass Spec (NIST)
- Not Available
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
- 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.
- Organic compounds
- Super Class
- Benzene and substituted derivatives
- Sub Class
- Direct Parent
- Alternative Parents
- Xanthines / 6-oxopurines / Alkaloids and derivatives / Benzylethers / Pyrimidones / Aryl chlorides / Vinylogous amides / Heteroaromatic compounds / Imidazoles / UreasTrialkylamines / Lactams / Dialkyl ethers / Azacyclic compounds / Organic salts / Organochlorides / Hydrocarbon derivatives / Organic oxides / Organopnictogen compounds show 9 more
- Diphenylmethane / Xanthine / 6-oxopurine / Purinone / Purine / Benzylether / Alkaloid or derivatives / Imidazopyrimidine / Pyrimidone / Aryl chlorideAryl halide / Pyrimidine / Azole / Heteroaromatic compound / Imidazole / Vinylogous amide / Lactam / Tertiary amine / Tertiary aliphatic amine / Urea / Dialkyl ether / Azacycle / Ether / Organoheterocyclic compound / Organic salt / Organic oxygen compound / Amine / Organic nitrogen compound / Hydrocarbon derivative / Organic oxide / Organopnictogen compound / Organooxygen compound / Organohalogen compound / Organochloride / Organonitrogen compound / Aromatic heteropolycyclic compound show 26 more
- Molecular Framework
- Not Available
- External Descriptors
- organic salt (CHEBI:4604)
- Pharmacological action
- 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
- Uniprot ID
- Uniprot Name
- Histamine H1 receptor
- Molecular Weight
- 55783.61 Da
Drug created on June 13, 2005 07:24 / Updated on October 21, 2018 20:28