Trimethobenzamide

Identification

Name
Trimethobenzamide
Accession Number
DB00662  (APRD01277)
Type
Small Molecule
Groups
Approved
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
Product Ingredients
IngredientUNIICASInChI Key
Trimethobenzamide HydrochlorideWDQ5P1SX7Q554-92-7WIIZEEPFHXAUND-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TiganInjection100 mg/mLIntramuscularPar Pharmaceutical2007-11-01Not applicableUs
TiganInjection, solution100 mg/mLIntramuscularGeneral Injectables & Vaccines2010-08-01Not applicableUs
TiganInjection100 mg/mLIntramuscularRebel Distributors2007-11-01Not applicableUs
TiganInjection100 mg/mLIntramuscularPar Pharmaceutical2007-11-01Not applicableUs
TiganCapsule300 mg/1OralPfizer Laboratories Div Pfizer Inc.2001-12-13Not applicableUs
TiganCapsule300 mg/1OralRemedy Repack2013-03-112017-01-11Us
Trimethobenzamide HydrochlorideInjection100 mg/mLIntramuscularPar Pharmaceutical2012-06-012016-12-31Us
Trimethobenzamide HydrochlorideInjection100 mg/mLIntramuscularRemedy Repack2014-01-09Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Trimethobenzamide HydrochlorideCapsule300 mg/1OralLake Erie Medical Dba Quality Care Produts Llc2010-07-13Not applicableUs
Trimethobenzamide HydrochlorideCapsule300 mg/1OralRemedy Repack2017-05-09Not applicableUs
Trimethobenzamide HydrochlorideCapsule300 mg/1OralA S Medication Solutions2003-08-282017-06-20Us
Trimethobenzamide HydrochlorideInjection, solution100 mg/mLIntramuscularGeneral Injectables & Vaccines2010-03-012017-01-25Us
Trimethobenzamide HydrochlorideCapsule300 mg/1OralLupin Pharmaceuticals2011-01-17Not applicableUs43386 0660 24 nlmimage10 d91decbf
Trimethobenzamide HydrochlorideCapsule300 mg/1OralA S Medication Solutions2011-01-172017-06-20Us
Trimethobenzamide HydrochlorideCapsule300 mg/1OralSun Pharmaceutical Industries Limited2003-08-28Not applicableUs
Trimethobenzamide HydrochlorideCapsule300 mg/1OralAvera Mc Kennan Hospital2015-07-16Not applicableUs
Trimethobenzamide HydrochlorideCapsule300 mg/1OralRemedy Repack2011-08-182016-11-08Us
Trimethobenzamide HydrochlorideCapsule300 mg/1Oralbryant ranch prepack2003-08-28Not applicableUs
International/Other Brands
Benzacot / Stemetic / Tebamide (GlaxoSmithKline) / Tribenzagan / Trimazide
Categories
UNII
W2X096QY97
CAS number
138-56-7
Weight
Average: 388.4574
Monoisotopic: 388.199822016
Chemical Formula
C21H28N2O5
InChI Key
FEZBIKUBAYAZIU-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.

Absorption

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

Volume of distribution
Not Available
Protein binding
Not 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.

Clearance
Not Available
Toxicity

Oral LD50 in mice is 1600 mg/kg.

Affected organisms
  • Humans and other mammals
Pathways
Not 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 Interactions
Not 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
Human Metabolome Database
HMDB14800
KEGG Compound
C07178
PubChem Compound
5577
PubChem Substance
46507787
ChemSpider
5375
ChEBI
27796
ChEMBL
CHEMBL1201256
PharmGKB
PA164764516
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Trimethobenzamide
ATC Codes
R06AA10 — Trimethobenzamide
FDA label
Download (36.7 KB)
MSDS
Download (73.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceHealthy Volunteers1
1CompletedBasic ScienceIdiopathic Parkinson's Disease1
4CompletedTreatmentAkinesia / Delayed Levadopa Onset / Delayed Levodopa 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.
Patents
Not Available

Properties

State
Solid
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
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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 n-benzylbenzamides. These are compounds containing a benzamide moiety that is N-linked to a benzyl group.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzoic acids and derivatives
Direct Parent
N-benzylbenzamides
Alternative Parents
Phenoxy compounds / Methoxybenzenes / Benzoyl derivatives / Anisoles / Alkyl aryl ethers / Trialkylamines / Secondary carboxylic acid amides / Amino acids and derivatives / Organopnictogen compounds / Organic oxides
show 1 more
Substituents
N-benzylbenzamide / Anisole / Benzoyl / Phenol ether / Methoxybenzene / Phenoxy compound / Alkyl aryl ether / Carboxamide group / Tertiary aliphatic amine / Tertiary amine
show 13 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
tertiary amino compound, benzamides (CHEBI:27796)

Drug created on June 13, 2005 07:24 / Updated on December 01, 2017 17:15