Identification

Summary

Trimethobenzamide is an antiemetic used to treat postoperative nausea and vomiting and nausea associated with gastroenteritis.

Brand Names
Tigan
Generic Name
Trimethobenzamide
DrugBank Accession Number
DB00662
Background

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.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 388.4574
Monoisotopic: 388.199822016
Chemical Formula
C21H28N2O5
Synonyms
  • N-[[4-(2-dimethylaminoethoxy)phenyl]methyl]-3,4,5-trimethoxybenzamide
  • Trimethobenzamide
  • Trimethobenzamidum
  • Trimetobenzamida

Pharmacology

Indication

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

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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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

Adverse Effects
Adverseeffects
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Toxicity

Oral LD50 in mice is 1600 mg/kg.

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
1,2-BenzodiazepineThe risk or severity of adverse effects can be increased when Trimethobenzamide is combined with 1,2-Benzodiazepine.
AcetazolamideThe risk or severity of adverse effects can be increased when Trimethobenzamide is combined with Acetazolamide.
AcetophenazineThe risk or severity of adverse effects can be increased when Trimethobenzamide is combined with Acetophenazine.
AclidiniumTrimethobenzamide may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.
AgomelatineThe risk or severity of adverse effects can be increased when Trimethobenzamide is combined with Agomelatine.
AlfentanilThe risk or severity of adverse effects can be increased when Trimethobenzamide is combined with Alfentanil.
AlimemazineThe risk or severity of adverse effects can be increased when Trimethobenzamide is combined with Alimemazine.
AlmotriptanThe risk or severity of adverse effects can be increased when Trimethobenzamide is combined with Almotriptan.
AlosetronThe risk or severity of adverse effects can be increased when Trimethobenzamide is combined with Alosetron.
AlprazolamThe risk or severity of adverse effects can be increased when Alprazolam is combined with Trimethobenzamide.
Interactions
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Food Interactions
  • Avoid alcohol. Ingestion of alcohol may increase the CNS depressant effects of trimethobenzamide causing drowsiness.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Trimethobenzamide hydrochlorideWDQ5P1SX7Q554-92-7WIIZEEPFHXAUND-UHFFFAOYSA-N
Product Images
International/Other Brands
Benzacot / Stemetic / Tebamide (GlaxoSmithKline) / Tribenzagan / Trimazide
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
TiganInjection100 mg/1mLIntramuscularPhysicians Total Care, Inc.1974-07-122008-05-01US flag
TiganCapsule300 mg/1OralPfizer Laboratories Div Pfizer Inc2001-12-132021-09-30US flag
TiganSuppository200 mg/1RectalMonarch Pharmaceuticals, Inc.2006-10-102006-10-10US flag
TiganInjection100 mg/1mLIntramuscularPar Pharmaceutical, Inc.2008-08-01Not applicableUS flag
TiganInjection100 mg/20mLIntramuscularMonarch Pharmaceuticals, Inc.2006-10-102006-10-10US flag
TiganInjection100 mg/1mLIntramuscularRebel Distributors2007-11-01Not applicableUS flag
TiganCapsule300 mg/1OralRemedy Repack2012-07-182015-05-28US flag
TiganInjection100 mg/20mLIntramuscularMonarch Pharmaceuticals, Inc.2006-11-152006-11-15US flag
TiganInjection100 mg/1mLIntramuscularGeneral Injectables & Vaccines, Inc2010-08-01Not applicableUS flag
TiganSuppository100 mg/1RectalPhysicians Total Care, Inc.1994-06-092007-05-01US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
TrimethobenzamideCapsule300 mg/1OralDirect_Rx2019-07-03Not applicableUS flag
Trimethobenzamide HydrochlorideCapsule300 mg/1OralAvera McKennan Hospital2015-07-162017-05-24US flag
Trimethobenzamide hydrochlorideCapsule300 mg/1OralActavis Totowa LLC2003-09-012008-08-20US flag
Trimethobenzamide HydrochlorideCapsule300 mg/1OralRemedy Repack2013-09-272014-09-27US flag
Trimethobenzamide HydrochlorideInjection100 mg/1mLIntramuscularRemedy Repack2014-01-032015-01-03US flag
Trimethobenzamide HydrochlorideCapsule300 mg/1OralA-S Medication Solutions2011-01-172018-03-31US flag50090 212220180913 8702 1gfk6ul
Trimethobenzamide HydrochlorideInjection, solution100 mg/1mLIntramuscularHospira, Inc.1987-04-032011-07-01US flag
Trimethobenzamide HydrochlorideCapsule300 mg/1OralA-S Medication Solutions2003-08-282017-11-08US flag
Trimethobenzamide HydrochlorideCapsule300 mg/1OralSun Pharmaceutical Industries Limited2003-08-28Not applicableUS flag
Trimethobenzamide HydrochlorideCapsule300 mg/1OralLupin Pharmaceuticals,Inc.2011-01-17Not applicableUS flag43386 0660 24 nlmimage10 d91decbf
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
EMEDUR 100 MG/20 MG SUPOZİTUAR, 5 ADETTrimethobenzamide hydrochloride (100 mg) + Benzocaine (20 mg)SuppositoryRectalSANOFİ SAĞLIK ÜRÜNLERİ LTD. ŞTİ.2020-08-14Not applicableTurkey flag
EMEDUR 200 MG SUPOZITUAR, 100 ADETTrimethobenzamide hydrochloride (200 mg) + Benzocaine (40 mg)SuppositoryRectalSANOFİ SAĞLIK ÜRÜNLERİ LTD. ŞTİ.2020-08-14Not applicableTurkey flag
EMEDUR 200 MG SUPOZITUAR, 5 ADETTrimethobenzamide hydrochloride (200 mg) + Benzocaine (40 mg)SuppositoryRectalSANOFİ SAĞLIK ÜRÜNLERİ LTD. ŞTİ.2020-08-14Not applicableTurkey flag
EMEDUR 200 MG SUPOZITUAR, 50 ADETTrimethobenzamide hydrochloride (200 mg) + Benzocaine (40 mg)SuppositoryRectalSANOFİ SAĞLIK ÜRÜNLERİ LTD. ŞTİ.2020-08-14Not applicableTurkey flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
TiganTrimethobenzamide hydrochloride (100 mg/1)SuppositoryRectalPhysicians Total Care, Inc.1994-06-092007-05-01US flag
Trimethobenzamide HydorchlorideTrimethobenzamide hydrochloride (100 mg/1)SuppositoryRectalPhysicians Total Care, Inc.2004-05-012007-09-07US flag
Trimethobenzamide HydorchlorideTrimethobenzamide hydrochloride (200 mg/1)SuppositoryRectalPhysicians Total Care, Inc.2004-03-012007-09-07US flag

Categories

ATC Codes
R06AA10 — Trimethobenzamide
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Alkyl aryl ether / Amine / Amino acid or derivatives / Anisole / Aromatic homomonocyclic compound / Benzoyl / Carboxamide group / Carboxylic acid derivative / Ether / Hydrocarbon derivative
show 13 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
tertiary amino compound, benzamides (CHEBI:27796)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
W2X096QY97
CAS number
138-56-7
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

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. [Article]
  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. [Article]
  3. FDA Approved Drug Products: TIGAN (trimethobenzamide hydrochloride) capsules [Link]
  4. FDA Approved Drug Products: TIGAN (trimethobenzamide hydrochloride) injection [Link]
Human Metabolome Database
HMDB0014800
KEGG Drug
D08643
KEGG Compound
C07178
PubChem Compound
5577
PubChem Substance
46507787
ChemSpider
5375
RxNav
38685
ChEBI
27796
ChEMBL
CHEMBL1201256
ZINC
ZINC000000538509
PharmGKB
PA164764516
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Trimethobenzamide
FDA label
Download (36.7 KB)
MSDS
Download (73.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentAkinesia / Delayed Levodopa Onset / Mobility decreased / Motor Symptoms / Parkinson's Disease (PD)1
4CompletedTreatmentParkinson's Disease (PD)1
1CompletedBasic ScienceHealthy Subjects (HS)1
1CompletedBasic ScienceIdiopathic Parkinson's Disease1

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
  • Actavis Group
  • A-S Medication Solutions LLC
  • C.O. Truxton Inc.
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • G & W Labs
  • Gipharmex SPA
  • H.J. Harkins Co. Inc.
  • Hospira Inc.
  • International Ethical Labs Inc.
  • Iopharm Laboratories Inc.
  • JHP Pharmaceuticals LLC
  • Kaiser Foundation Hospital
  • King Pharmaceuticals Inc.
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Monarch Pharmacy
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mutual Pharmaceutical Co.
  • Nucare Pharmaceuticals Inc.
  • Paddock Labs
  • PD-Rx Pharmaceuticals Inc.
  • Pecos Pharmaceutical Inc.
  • Perrigo Co.
  • Pharmedix
  • Physician Partners Ltd.
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Qualitest
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Shire Inc.
  • Southwood Pharmaceuticals
  • Spectrum Pharmaceuticals
  • Stat Rx Usa
  • Veratex Corp.
Dosage Forms
FormRouteStrength
Solution / dropsOral
SuppositoryRectal
Tablet, film coated
Injection, solutionIntramuscular
Tablet, coated
InjectionIntramuscular100 mg/20mL
InjectionIntramuscular100 mg/1mL
InjectionIntramuscular100 mg/2mL
SuppositoryRectal100 mg/1
SuppositoryRectal200 mg/1
CapsuleOral300 mg/1
Injection, solutionIntramuscular100 mg/1mL
Injection, solutionIntramuscular200 mg/1mL
SuppositoryRectal
InjectionIntramuscular
CapsuleOral
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

Drug created at June 13, 2005 13:24 / Updated at August 13, 2021 20:47