D2 receptor[1]

Trimethobenzamide is a benzamide antiemetic (non-phenothiazine) that inhibits the medullary chemoreceptor trigger zone by preventing emetic impulses to the vomiting center. It works by centrally blocking D2 receptors[1].

Trimethobenzamide has an oral bioavailability of 60% to 100%. After oral administration, the time to peak is around 45 minutes, and after intramuscular (IM) administration, it is approximately 30 minutes[1].

Absorption, Distribution and Excretion
The relative bioavailability of the capsule formulation compared to the solution is 100%.
Between 30 – 50% of a single dose in humans is excreted unchanged in the urine within 48–72 hours.
CONCN IN BLOOD WAS 0.1-0.2 MG% AFTER ORAL ADMIN OF 0.5 MG/KG OF TRIMETHOBENZAMIDE. /FROM TABLE/
IN MAN, APPROX 30 TO 50% OF...DOSE IS EXCRETED IN URINE AS INTACT DRUG WITHIN 48 TO 72 HR; 20% OF...DOSE IS EXCRETED DURING FIRST 24 HR. IN DOGS, /DRUG/ IS DISTRIBUTED IN LIVER, KIDNEY AND LUNG...DRUG & /N-DESMETHYL & N-OXIDE DERIV/ EXCRETED IN URINE AND BILE
IN ADULTS, FOLLOWING ORAL OR RECTAL ADMIN OF 500 MG...AVG PEAK BLOOD LEVELS OF FREE DRUG /WERE 1-2 MCG/ML/. ...GENERALLY CLEARED FROM THE BLOOD WITHIN 2 HR...MEASURABLE CONCN MAY PERSIST FOR OVER 24 HR /HUMAN/

---

Metabolism / Metabolites
Hepatic.
METABOLIZED IN THE LIVER OF THE DOG TO THE N-DESMETHYL AND N-OXIDE DERIVATIVES. ...IN /HUMAN/ ADULTS, FOLLOWING ORAL OR RECTAL ADMIN OF 500 MG...AN UNIDENTIFIED METABOLITE HAS BEEN DEMONSTRATED.

---

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

Hepatotoxicity
Serum aminotransferase elevations during trimethobenzamide therapy are uncommon and rates of such elevations have not been reported in large clinical trials. A single case report of hepatitis and jaundice attributed to trimethobenzamide was published in 1967 that predated availability of tests for hepatitis A, B and C and of modern imaging studies. The latency to onset was approximately 2 weeks and the pattern of injury was mixed. There were no immunoallergic or autoimmune features and recovery was prompt once the medication was stopped. Since that report, there has only been a single mention of possible hepatotoxicity due to trimethobenzamide, a somewhat prolonged case of hepatocellular injury with a cholestatic pattern on liver biopsy despite minimal jaundice. Thus, clinically apparent liver injury from trimethobenzamide must be very rare and is generally mild and self-limited in course.
Likelihood score: D (possible rare cause of clinically apparent liver injury).

---

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because no information is available on the continuous use of trimethobenzamide during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. Occasional, short-term use of trimethobenzamide for the treatment of nausea and vomiting appears to be acceptable.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

[1]. Smith HS, et al. Dopamine receptor antagonists. Ann Palliat Med. 2012 Jul;1(2):137-42.

Trimethobenzamide is the amide obtained by formal condensation of 3,4,5-trihydroxybenzoic acid with 4-[2-(N,N-dimethylamino)ethoxy]benzylamine. It is used to prevent nausea and vomitting in humans. It has a role as an antiemetic. It is a tertiary amino compound and a member of benzamides.
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.
Trimethobenzamide is an Antiemetic. The physiologic effect of trimethobenzamide is by means of Emesis Suppression.
Trimethobenzamide is an orally available, antiemetic agent used in the therapy of nausea and vomiting associated with medications and gastrointestinal, viral and other illnesses. Trimethobenzamide has not been linked convincingly to elevations in serum enzymes during therapy and despite widescale use for almost 50 years, it has rarely been linked to instances of clinically apparent liver injury with jaundice.
See also: Trimethobenzamide Hydrochloride (has salt form).

---

Drug Indication
For the treatment of postoperative nausea and vomiting and for nausea associated with gastroenteritis.
FDA Label

---

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.
DRUG...SHOWN TO INHIBIT STIMULI @ CHEMORECEPTOR TRIGGER ZONE IN ANIMALS... /HYDROCHLORIDE SALT/

---

Therapeutic Uses
Antiemetics
ITS ANTIEMETIC POTENCY IS ABOUT ONE-TENTH THAT OF CHLORPROMAZINE WHEN GIVEN SC & ONE-FOURTH THAT OF LATTER WHEN GIVEN ORALLY. /HYDROCHLORIDE SALT/
...HAS LITTLE OR NO VALUE IN PREVENTION & TREATMENT OF MOTION SICKNESS. /HYDROCHLORIDE SALT/
STUDY OF TRIMETHOBENZAMIDE HYDROCHLORIDE SUPPOSITORIES IN TREATMENT OF NAUSEA & VOMITING IN CHILDREN. RESULTS INDICATE THAT THEY ARE NO MORE EFFECTIVE THAN PLACEBO FOR TREATMENT OF VOMITING ASSOC WITH GASTRITIS, PT TREATED FOR NAUSEA REPORTED RELIEF.
MEDICATION (VET): ANTIEMETIC /HYDROCHLORIDE SALT/

---

Drug Warnings
IN PT WITH ACUTE FEBRILE, ILLNESS, ENCEPHALITIDES, GASTROENTERITIS, DEHYDRATION, & ELECTROLYTE IMBALANCE (ESP IN CHILDREN & ELDERLY & DEBILITATED) CNS REACTIONS SUCH AS OPISTHOTONOS, CONVULSIONS, COMA, & EXTRAPYRAMIDAL SYMPTOMS...BUT IT IS NOT CERTAIN THAT THESE EFFECTS WERE IN ALL CASES DUE TO...DRUG. /HYDROCHLORIDE SALT/
...CAUTION SHOULD BE EXERCISED WHEN TRIMETHOBENZAMIDE HYDROCHLORIDE IS USED... /IN PT WITH ACUTE FEBRILE ILLNESS, ENCEPHALITIDES, GASTROENTERITIS, DEHYDRATION, & ELECTROLYTE IMBALANCE (ESP IN CHILDREN & ELDERLY & DEBILITATED/. /HYDROCHLORIDE SALT/
USE OF INJECTABLE FORM OF DRUG IN CHILDREN, SUPPOSITORIES IN PREMATURE OR NEWBORN INFANTS, & USE OF DRUG IN PT HYPERSENSITIVE TO IT ARE CONTRAINDICATED. ALSO, SUPPOSITORIES SHOULD NOT BE USED IN PT KNOWN TO BE SENSITIVE TO BENZOCAINE OR SIMILAR TYPES OF LOCAL ANESTHETICS. /HYDROCHLORIDE SALT/
CAUTION IS REQUIRED IN USE OF ALL ANTIEMETICS BECAUSE THEY MAY MASK SYMPTOMS OF ORGANIC DISEASE (EG, GI OR CNS DISORDERS) OR TOXIC EFFECTS OF OTHER DRUGS. ... INDIVIDUALS WHOSE ACTIVITIES REQUIRE ALERTNESS...SHOULD USE ANTIEMETICS WITH GREAT CAUTION. /ANTIEMETICS/

---

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.

C21H28N2O5

388.45742

388.2

138-56-7

Trimethobenzamide hydrochloride;554-92-7;Trimethobenzamide-d6

5577

Typically exists as solid at room temperature

1.131 g/cm3

506.9ºC at 760 mmHg

260.4ºC

2.13E-10mmHg at 25°C

2.973

1

6

10

28

440

0

CN(CCOC1=CC=C(CNC(C2=CC(OC)=C(OC)C(OC)=C2)=O)C=C1)C

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)

N-[[4-[2-(dimethylamino)ethoxy]phenyl]methyl]-3,4,5-trimethoxybenzamide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

---

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

View More

Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

View More

Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

 (Please use freshly prepared in vivo formulations for optimal results.)