TRIMETHOBENZAMIDE

First approved in 1959

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H28N2O5
Molecular Weight	388.4574
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC(=CC(OC)=C1OC)C(=O)NCC2=CC=C(OCCN(C)C)C=C2

InChI

InChIKey=FEZBIKUBAYAZIU-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/017530s024lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/017531s014lbl.pdf | http://www.sciencedirect.com/science/article/pii/B9781416002086500231 | https://www.ncbi.nlm.nih.gov/pubmed/23002952

Trimethobenzamide (trade names Tebamide, Tigan) is an antiemetic used to prevent nausea and vomiting. Trimethobenzamide is an antagonist of the D2 receptor, that affects the chemoreceptor trigger zone (CTZ) of the medulla oblongata to suppress nausea and vomiting. The oral bioavailability of trimethobenzamide is 60% to 100%. The time to peak is about 45 minutes after oral administration and; I.M. about 30 minutes after intramuscular administration. The onset action of trimethobenzamide for antiemetic effects is 10-40 minutes after oral administration and; 15-35 minutes after intramuscular administration. The duration of action is 3-4 hours. Trimethobenzamide is generally considered the most potent antiemetic that does not have effects on the serotonergic, dopaminergic, or histaminergic systems, so it has a lower likelihood of causing undesired side effects. Possible side effects include drowsiness, dizziness, headache, diarrhea, muscle cramps, and blurred vision. More serious adverse effects include skin rash, tremors, parkinsonism, and jaundice.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dopamine D2 receptor 297 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25841474	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Postoperative nausea and vomiting 29 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/017531s014lbl.pdf	Primary		Approved 8429	TIGAN Approved Use INDICATIONS & USAGE Tigan is indicated for the treatment of postoperative nausea and vomiting and for nausea associated with gastroenteritis. Launch Date 1974
Nausea associated with gastroenteritis 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/017530s024lbl.pdf	Primary		Approved 8429	TIGAN Approved Use INDICATIONS & USAGE Tigan is indicated for the treatment of postoperative nausea and vomiting and for nausea associated with gastroenteritis. Launch Date 1974

C_max

Value	Dose	Analyte	Population
3536 ng/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3817 ng/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3847 ng/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4219 ng/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
3712 ng/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	200 mg single, intramuscular dose: 200 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3729 ng/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	200 mg single, intramuscular dose: 200 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3537 ng/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	200 mg single, intramuscular dose: 200 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4002 ng/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	200 mg single, intramuscular dose: 200 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
3982 ng/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	200 mg single, intramuscular dose: 200 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
5211 ng/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3863 ng/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
10041 ng × h/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
10218 ng × h/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
10371 ng × h/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
10436 ng × h/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
10448 ng × h/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	200 mg single, intramuscular dose: 200 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
10465 ng × h/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	200 mg single, intramuscular dose: 200 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
10581 ng × h/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	200 mg single, intramuscular dose: 200 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
10621 ng × h/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	200 mg single, intramuscular dose: 200 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
11544 ng × h/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	200 mg single, intramuscular dose: 200 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
13647 ng × h/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
9768 ng × h/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
7.8 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7.8 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
8 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
7.8 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
6.8 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	200 mg single, intramuscular dose: 200 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
6.8 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	200 mg single, intramuscular dose: 200 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
7 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	200 mg single, intramuscular dose: 200 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.7 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	200 mg single, intramuscular dose: 200 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
6.5 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	200 mg single, intramuscular dose: 200 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
7.4 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
7.6 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/017531_S010_TIGAN_CAPSULE_AP.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	TRIMETHOBENZAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://link.springer.com/chapter/10.1007/978-3-319-98343-1_38 Page: 132.0

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B3-045980	http://www.3bsc.com/index/pro_info.php?id=82579
AA Blocks	AA00I9T1	https://www.aablocks.com/goods/Goods/detail?id=AA00I9T1
AHH Chemical co.,ltd	MT-59937	http://www.ahhchemical.com/product/MT-59937.html
AK Scientific, Inc. (AKSCI)	V1615	http://www.aksci.com/item_detail.php?cat=V1615
Aaron Chemicals	AR00IAKT	http://www.aaronchem.com/554-92-7
Alfa Chemistry	AP554927	https://reagents.alfa-chemistry.com/product/trimethobenzamide-hydrochloride-cas-554-92-7-13070.html
Alichem	19140697	http://www.alichem.com/en/products/554-92-7.html
Ambeed	A148362	https://www.ambeed.com/products/554-92-7.html
Angel Pharmatech	AG-10884	http://www.angelpharmatech.com/554-92-7.html
Ark Pharm	AK140655	http://www.arkpharminc.com/products/554-92-7.html
BLD Pharm	BD155412	http://www.bldpharm.com/products/554-92-7.html
BOC Sciences	554-92-7	https://www.bocsci.com/trimethobenzamide-hydrochloride-cas-554-92-7-item-124935.html
CSNpharm	CSN23250	https://www.csnpharm.com/products/trimethobenzamide-hcl.html
Chem Scene	CS-7696	http://www.chemscene.com/554-92-7.html
ChemMol	99105043	http://www.chemmol.com/chemmol/99105043.html
Chemspace	CSSB00000087811	https://chem-space.com/CSSB00000087811
Clearsynth	CS-T-62450	https://www.clearsynth.com/en/CST62450.html
Combi-Blocks	QW-6647	http://www.combi-blocks.com/cgi-bin/find.cgi?QW-6647
Finetech	FT-0736653	http://www.finetechnology-ind.com/prod/detail/pub/554-92-7.html
LGC Standards	LGCFOR3281.00	https://www.lgcstandards.com/US/en/p/LGCFOR3281.00
LGC Standards	MM3281.00	https://www.lgcstandards.com/US/en/p/MM3281.00
Lab Network	LN01309622	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01309622
MedChem Express	HY-12751A	https://www.medchemexpress.com/Trimethobenzamide_hydrochloride.html
MolPort	MolPort-003-666-301	https://www.molport.com/shop/molecule-link/MolPort-003-666-301
Molcore	MC560181	https://www.molcore.com/product/554-92-7
OChem	30706	http://www.ocheminc.com/index.php?act=psearch&pid=554T927
Selleck Chemicals	S5483	http://www.selleckchem.com/products/trimethobenzamide-hydrochloride.html
Smolecule	S545892	http://www.smolecule.com/products/s545892
TCI (Tokyo Chemical Industry)	T3525	http://www.tcichemicals.com/eshop/en/us/commodity/T3525/index.html
THE BioTek	bt-287008	https://www.thebiotek.com/product/inhibitors/bt-287008
abcr GmbH	AB506024	http://www.abcr.de/shop/en/AB506024
eNovation Chemicals	D673676	https://www.enovationchem.com/ProductDetails.asp?ProductID=D673676
eNovation Chemicals	D765721	https://www.enovationchem.com/ProductDetails.asp?ProductID=D765721
mcule	MCULE-6632962832	https://mcule.com/MCULE-6632962832/

PubMed

Title	Date	PubMed
Studies of drugs given before anaesthesia. X. Two non-phenothiazine anti-emetics--cyclizine and trimethobenzamide.	1966 Jan	5908416
Trimethobenzamide HCl in the treatment of nausea and vomiting associated with antineoplastic chemotherapy.	1980 May-Jun	7400373
Prune belly syndrome and heart defect in one of monozygotic twins, following exposure to Tigan and Bendectin.	1985	4050288
Intranasal apomorphine rescue therapy for parkinsonian "off" periods.	1996 Jun	8726538
Trimethobenzamide in elderly patients.	2004 Jun	15182103
Practical considerations in the use of apomorphine injectable.	2004 Mar 23	15037670
Rapid treatment of "wearing off" in Parkinson's disease.	2004 Mar 23	15037669
Anesthesiologists' practice patterns for treatment of postoperative nausea and vomiting in the ambulatory Post Anesthesia Care Unit.	2006 Jun 1	16740165
FDA halts sales of some anti-vomiting suppositories...and are cough medications effective in children?	2007 May	17595688
Use of antiemetic agents in acute gastroenteritis: a systematic review and meta-analysis.	2008 Sep	18762604
Vestibulocochlear toxicity in a pair of siblings 15 years apart secondary to aspartame: two case reports.	2009 Sep 15	20126318
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.	2010 Dec	21818443

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult intramuscular dosage: 2 mL (200 mg) t.i.d. or q.i.d. . Usual Adult oral dosage: 300 mg orally three or four times daily. Usual Adult Rectal dosage: 200 mg 3-4 times a day.

Route of Administration: Other

In Vitro Use Guide

Rat embryos were used for activity evaluation. Embryos were explanted on day 9.5 of gestation and cultured. Whole rat serum was used as a culture medium for the control group while different concentrations of dimenhydrinate (2.5–20 lg/ml), metoclopramide (10–50 lg/ml) and trimethobenzamide HCl (25–100 lg/ml) were added to serum for the experimental groups.

Name

Type

Language

TRIMETHOBENZAMIDE

Official Name

English

AMETIK DAMLA

Brand Name

English

TRIMETHOBENZAMIDE [MI]

Common Name

English

Trimethobenzamide [WHO-DD]

Common Name

English

TRIMETHOBENZAMIDE [HSDB]

Common Name

English

TRIMETHOBENZAMIDE [VANDF]

Common Name

English

trimethobenzamide [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C267