Trimethobenzamide

388.46

388.46

205-332-1

W2X096QY97

DTXSID8023711

R - Respiratory system

2924299090

69.3

2.2

Solid

1.131 g/cm3

188.7 °C

506.9ºC at 760 mmHg

260.4ºC

3.98e-02 g/L

2.13E-10mmHg at 25°C

8.78None

8.78

CRYSTALS; MP: 187.5-190 °C; FREELY SOL IN WATER (MORE THAN 50% @ 25 °C) /HYDROCHLORIDE/

PHARMACOLOGY.[BLESSEL ET AL; ANAL PROFILES DRUG SUBST 2: 551 (1973)]

Oral LD50 in mice is 1600 mg/kg.

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.

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

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.

Gastrointestinal Agents

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/

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/

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.

Drugs used to prevent NAUSEA or VOMITING. (See all compounds classified as Antiemetics.)

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/

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.

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

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/

...WITH LARGER DOSES, DROWSINESS, VERTIGO, DIARRHEA, CUTANEOUS HYPERSENSITIVITY REACTIONS, EXTRAPYRAMIDAL REACTIONS, & EXAGGERATION OF PRE-EXISTING NAUSEA HAVE OCCURRED. PAIN @ SITE OF INJECTION & LOCAL IRRITATION AFTER RECTAL ADMIN HAVE BEEN NOTED. /HYDROCHLORIDE SALT/|CASE REPORT. 2-WK-OLD MALE INFANT WAS WELL UNTIL 7 DAYS PRIOR TO ADMISSION. HE RECEIVED 3 RECTAL 100 MG DOSES IN 24 HR PERIOD PRIOR TO ADMISSION. HE BECAME LISTLESS, HYPOTONIC & CYANOTIC. EXTRAPYRAMIDAL REACTION SECONDARY TO DRUG WAS DIAGNOSIS.|DURING YR 1959-1966, TRIMETHOBENZAMIDE PRESCRIBED TO 11,481 PREGNANT WOMEN FOR NAUSEA & VOMITING IN 1ST 84 DAYS OF PREGNANCY, WAS EVALUATED FOR TERATOGENIC POTENTIAL. THERE WAS SLIGHT SUGGESTION OF EXCESS OF SEVERE CONGENITAL ANOMALIES.|HEPATITIS FOLLOWING THE ADMIN OF TRIMETHOBENZAMIDE HYDROCHLORIDE.

T-Gen

TIGAN (BEECHAM). INJECTION: SOLN 100 MG/ML IN 2 & 20 ML CONTAINERS. ORAL: CAPSULES 100 & 250 MG. RECTAL: SUPPOSITORIES 100 (PEDIATRIC) & 200 MG (WITH 2% BENZOCAINE) /HYDROCHLORIDE SALT/|RO 2-9578; ANAUS, EMAMIN; NAUSETON; TIGAN; XAMETINA /HYDROCHLORIDE/|TIGAN HYDROCHLORIDE; TRIMETHOBENZAMIDE HYDROCHLORIDE; N-(P-(2-DIMETHYLAMINO)ETHOXY)BENZYL)-3,4,5-TRIMETHOXYBENZAMIDE HYDROCHLORIDE; 4-(2-DIMETHYLAMINOETHOXY)-N-(3,4,5-TRIMETHOXYBENZOYL)BENZYLAMINE HYDROCHLORIDE. MOL FORMULA: C21-H28-N2-O5.CL-H /HYDROCHLORIDE/

A 5% AQ SOLN IS STABLE TO AUTOCLAVING @ 120 °C FOR 20 MIN @ PH 3-7. /HYDROCHLORIDE SALT/

TLC OF TRIMETHOBENZAMIDE.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients