Identification
NameTrimethobenzamide
Accession NumberDB00662  (APRD01277)
TypeSmall Molecule
GroupsApproved
Description

Trimethobenzamide is a novel antiemetic which prevents nausea and vomiting in humans. Its actions are unclear but most likely involves the chemoreceptor trigger zone (CTZ). In dogs pretreated with trimethobenzamide HCl, the emetic response to apomorphine is inhibited, while little or no protection is afforded against emesis induced by intragastric copper sulfate.

Structure
Thumb
Synonyms
N-[[4-(2-Dimethylaminoethoxy)phenyl]methyl]-3,4,5-trimethoxybenzamide
Trimethobenzamidum
Trimetobenzamida
External IDs Not Available
Product Ingredients
IngredientUNIICASInChI KeyDetails
Trimethobenzamide HydrochlorideWDQ5P1SX7Q 554-92-7WIIZEEPFHXAUND-UHFFFAOYSA-NDetails
Product Images
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TiganInjection100 mg/mLIntramuscularRebel Distributors2007-11-01Not applicableUs
TiganInjection, solution100 mg/mLIntramuscularGeneral Injectables & Vaccines2010-08-01Not applicableUs
TiganInjection100 mg/mLIntramuscularPar Pharmaceutical2007-11-01Not applicableUs
TiganCapsule300 mg/1OralRemedy Repack2013-03-112017-01-11Us
TiganCapsule300 mg/1OralPfizer Laboratories Div Pfizer Inc.2001-12-13Not applicableUs
TiganInjection100 mg/mLIntramuscularPar Pharmaceutical2007-11-01Not applicableUs
Trimethobenzamide HydrochlorideInjection100 mg/mLIntramuscularPar Pharmaceutical2012-06-012016-12-31Us
Trimethobenzamide HydrochlorideInjection100 mg/mLIntramuscularRemedy Repack2014-01-09Not applicableUs
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Trimethobenzamide HydrochlorideCapsule300 mg/1OralRebel Distributors2003-08-28Not applicableUs
Trimethobenzamide HydrochlorideCapsule300 mg/1Oralbryant ranch prepack2003-08-28Not applicableUs
Trimethobenzamide HydrochlorideCapsule300 mg/1OralA S Medication Solutions2003-08-282017-06-20Us
Trimethobenzamide HydrochlorideCapsule300 mg/1OralRemedy Repack2011-08-182016-11-08Us
Trimethobenzamide HydrochlorideCapsule300 mg/1OralRemedy Repack2017-05-09Not applicableUs
Trimethobenzamide HydrochlorideCapsule300 mg/1OralPhysicians Total Care, Inc.2007-01-05Not applicableUs
Trimethobenzamide HydrochlorideCapsule300 mg/1OralA S Medication Solutions2011-01-172017-06-20Us
Trimethobenzamide HydrochlorideCapsule300 mg/1OralLake Erie Medical Dba Quality Care Produts Llc2010-07-13Not applicableUs
Trimethobenzamide HydrochlorideInjection, solution100 mg/mLIntramuscularGeneral Injectables & Vaccines2010-03-012017-01-25Us
Trimethobenzamide HydrochlorideCapsule300 mg/1OralAvera Mc Kennan Hospital2015-07-16Not applicableUs
Trimethobenzamide HydrochlorideCapsule300 mg/1OralA S Medication Solutions2011-01-172017-06-20Us
Trimethobenzamide HydrochlorideCapsule300 mg/1OralGavis Pharmaceuticals, LLC.2011-01-17Not applicableUs43386 0660 24 nlmimage10 d91decbf
Trimethobenzamide HydrochlorideCapsule300 mg/1OralMutual Pharmaceutical2003-08-28Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
BenzacotNot Available
StemeticNot Available
TebamideGlaxoSmithKline
TribenzaganNot Available
TrimazideNot Available
Brand mixturesNot Available
Categories
UNIIW2X096QY97
CAS number138-56-7
WeightAverage: 388.4574
Monoisotopic: 388.199822016
Chemical FormulaC21H28N2O5
InChI KeyFEZBIKUBAYAZIU-UHFFFAOYSA-N
InChI
InChI=1S/C21H28N2O5/c1-23(2)10-11-28-17-8-6-15(7-9-17)14-22-21(24)16-12-18(25-3)20(27-5)19(13-16)26-4/h6-9,12-13H,10-11,14H2,1-5H3,(H,22,24)
IUPAC Name
N-({4-[2-(dimethylamino)ethoxy]phenyl}methyl)-3,4,5-trimethoxybenzamide
SMILES
COC1=CC(=CC(OC)=C1OC)C(=O)NCC1=CC=C(OCCN(C)C)C=C1
Pharmacology
Indication

For the treatment of postoperative nausea and vomiting and for nausea associated with gastroenteritis.

Structured Indications
Pharmacodynamics

Trimethobenzamide is a novel antiemetic which prevents nausea and vomiting in humans. Its actions are unclear but most likely involves the chemoreceptor trigger zone (CTZ). In dogs pretreated with trimethobenzamide HCl, the emetic response to apomorphine is inhibited, while little or no protection is afforded against emesis induced by intragastric copper sulfate.

Mechanism of action

The mechanism of action of trimethobenzamide as determined in animals is obscure, but may involve the chemoreceptor trigger zone (CTZ), an area in the medulla oblongata through which emetic impulses are conveyed to the vomiting center; direct impulses to the vomiting center apparently are not similarly inhibited.

Related Articles
Absorption

The relative bioavailability of the capsule formulation compared to the solution is 100%.

Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic.

Route of elimination

Between 30 – 50% of a single dose in humans is excreted unchanged in the urine within 48–72 hours.

Half life

The mean elimination half-life of trimethobenzamide is 7 to 9 hours.

ClearanceNot Available
Toxicity

Oral LD50 in mice is 1600 mg/kg.

Affected organisms
  • Humans and other mammals
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
EthanolEthanol may increase the central nervous system depressant (CNS depressant) activities of Trimethobenzamide.Approved
Food InteractionsNot Available
References
Synthesis Reference

Vittorio Rossetti, Alessandro Dondoni, Giancarlo Fantin, "N-(4-Hydroxybenzyl)-3,4,5-trimethoxybenzamide and method for producing trimethobenzamide chlorohydrate." U.S. Patent US4507499, issued December, 1969.

US4507499
General References
  1. Hurley JD, Eshelman FN: Trimethobenzamide HCl in the treatment of nausea and vomiting associated with antineoplastic chemotherapy. J Clin Pharmacol. 1980 May-Jun;20(5-6 Pt 1):352-6. [PubMed:7400373 ]
  2. Dundee JW, Halliday F, Nicholl RM, Moore J: Studies of drugs given before anaesthesia. X. Two non-phenothiazine anti-emetics--cyclizine and trimethobenzamide. Br J Anaesth. 1966 Jan;38(1):50-7. [PubMed:5908416 ]
External Links
ATC CodesR06AA10 — Trimethobenzamide
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (36.7 KB)
MSDSDownload (73.5 KB)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceHealthy Volunteers1
1CompletedBasic ScienceIdiopathic Parkinson's Disease1
4CompletedTreatmentAkinesia / Delayed Levadopa Onset / Mobility decreased / Motor Symptoms / Parkinson's Disease (PD)1
4CompletedTreatmentParkinson's Disease (PD)1
Pharmacoeconomics
Manufacturers
  • King pharmaceuticals inc
  • Actavis totowa llc
  • Mutual pharmacal co
  • Jhp pharmaceuticals llc
  • Hospira inc
  • Smith and nephew solopak div smith and nephew
  • Solopak medical products inc
  • Watson laboratories inc
Packagers
Dosage forms
FormRouteStrength
InjectionIntramuscular100 mg/mL
Injection, solutionIntramuscular100 mg/mL
CapsuleOral300 mg/1
Prices
Unit descriptionCostUnit
Trimethobenzamide hcl powder44.24USD g
Tigan 100 mg/ml vial7.06USD ml
Trimethobenzamide HCl 300 mg capsule1.7USD capsule
Tigan 300 mg capsule1.52USD capsule
Trimethobenzamide 100 mg/ml1.47USD ml
Trimethobenzamide 250 mg cap1.1USD each
Trimethobenzamide 300 mg cap0.99USD each
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point (°C)188.7 °CPhysProp
water solubility40 mg/LNot Available
logP2.29EL TAYER,N ET AL. (1985)
pKa8.78EL TAYAR,N ET AL. (1985)
Predicted Properties
PropertyValueSource
Water Solubility0.0398 mg/mLALOGPS
logP2.44ALOGPS
logP2.16ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)14.36ChemAxon
pKa (Strongest Basic)8.77ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area69.26 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity108.52 m3·mol-1ChemAxon
Polarizability43.19 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9898
Blood Brain Barrier+0.8121
Caco-2 permeable+0.6907
P-glycoprotein substrateSubstrate0.6855
P-glycoprotein inhibitor IInhibitor0.6152
P-glycoprotein inhibitor IINon-inhibitor0.5571
Renal organic cation transporterNon-inhibitor0.6259
CYP450 2C9 substrateNon-substrate0.7472
CYP450 2D6 substrateNon-substrate0.6388
CYP450 3A4 substrateSubstrate0.7204
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8188
Ames testNon AMES toxic0.7153
CarcinogenicityNon-carcinogens0.7638
BiodegradationNot ready biodegradable0.9285
Rat acute toxicity2.3338 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9673
hERG inhibition (predictor II)Non-inhibitor0.6758
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as n-benzylbenzamides. These are compounds containing a benzamide moiety that is N-linked to a benzyl group.
KingdomChemical entities
Super ClassOrganic compounds
ClassBenzenoids
Sub ClassBenzene and substituted derivatives
Direct ParentN-benzylbenzamides
Alternative ParentsPhenoxy compounds / Methoxybenzenes / Benzoyl derivatives / Anisoles / Alkyl aryl ethers / Trialkylamines / Secondary carboxylic acid amides / Amino acids and derivatives / Organopnictogen compounds / Organic oxides
SubstituentsN-benzylbenzamide / Anisole / Benzoyl / Phenol ether / Methoxybenzene / Phenoxy compound / Alkyl aryl ether / Carboxamide group / Tertiary aliphatic amine / Tertiary amine
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptorstertiary amino compound, benzamides (CHEBI:27796 )
Drug created on June 13, 2005 07:24 / Updated on July 18, 2017 16:51