D₂ receptor

Trimethobenzamide 是一种（非吩噻嗪）苯甲酰胺止吐药，可中枢阻断 D2 受体，从而通过阻断呕吐中枢的催吐冲动来抑制髓质化学感受器触发区 [1]。

Trimethobenzamide 的口服生物利用度为 60% 至 100%。口服给药后约45分钟达到峰值；肌内给药后约30分钟进行肌内(IM)给药[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/

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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.

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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).

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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]. 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).

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

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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/

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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/

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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/

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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.

C21H29CLN2O5

424.9184

424.176

C, 59.36; H, 6.88; Cl, 8.34; N, 6.59; O, 18.83

554-92-7

Trimethobenzamide; 138-56-7; Trimethobenzamide-d6

5577

White to off-white solid powder

1.131g/cm3

506.9ºC at 760mmHg

187.5-190°

3.775

69.26

1

6

10

28

440

0

Cl[H].O(C1C([H])=C([H])C(=C([H])C=1[H])C([H])([H])N([H])C(C1C([H])=C(C(=C(C=1[H])OC([H])([H])[H])OC([H])([H])[H])OC([H])([H])[H])=O)C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])[H]

WIIZEEPFHXAUND-UHFFFAOYSA-N

InChI=1S/C21H28N2O5.ClH/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);1H

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

Ro-2-9578; Ro-2 9578; Ro 2 9578; Tebamide; Ticon; Tigan; trimethobenzamide; trimethobenzamide monohydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

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

DMSO: ≥ 100 mg/mL (~235.3 mM)

配方 1 中的溶解度: ≥ 2.5 mg/mL (5.88 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (5.88 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (5.88 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。