D2 receptor[1]

Trimethobenzamide 是一种苯甲酰胺止吐药（非吩噻嗪），通过防止呕吐中枢的催吐冲动来抑制髓质化学感受器触发区。它通过集中阻断 D2 受体发挥作用[1]。

Trimethobenzamide 的口服生物利用度为 60% 至 100%。口服给药后，达峰时间约为45分钟，肌注(IM)给药后，达峰时间约为30分钟[1]。

Absorption, Distribution and Excretion
The relative bioavailability of capsules is 100% compared to solutions. Following a single human dose, 30% to 50% of the drug is excreted unchanged in the urine within 48 to 72 hours. After oral administration of 0.5 mg/kg tricresylformamide, the plasma concentration is 0.1–0.2 mg%. (Data from table) In humans, approximately 30% to 50% of the dose is excreted unchanged in the urine within 48 to 72 hours; 20% of the dose is excreted within the first 24 hours. In dogs, the drug is distributed to the liver, kidneys, and lungs… The drug and its N-demethyl and N-oxide derivatives are excreted in the urine and bile. After oral or rectal administration of 500 mg in adults… the mean peak plasma concentration of the free drug is 1–2 μg/mL. …It is usually cleared from the blood within 2 hours… Measurable concentrations may persist for more than 24 hours.

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Metabolism/Metabolites
Hepatic metabolism.
In canine liver, it is metabolized to N-demethyl and N-oxide derivatives. …In adults, after oral or rectal administration of 500 mg…an unidentified metabolite has been identified.

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

Hepatotoxicity
Elevated serum transaminase levels during trimetobenzamide treatment are uncommon, and no such elevations have been reported in large clinical trials. A case report of hepatitis and jaundice caused by trimetobenzamide was published in 1967, before hepatitis A, B, and C testing and modern imaging techniques were widely available. The incubation period in this case was approximately two weeks, and the injury pattern was mixed. The patient had no immune allergies or autoimmune characteristics and recovered rapidly after discontinuation of the drug. Since that report, only one case has been mentioned as potentially causing hepatotoxicity with trimetobenzamide. This case presented with prolonged hepatocellular damage, cholestatic liver biopsy, but mild jaundice. Therefore, clinically significant liver injury caused by trimetobenzamide is very rare, and symptoms are usually mild and resolve spontaneously. Probability Score: D (Possibly a rare cause of clinically significant liver injury).

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Effects during pregnancy and lactation
◉ Overview of medication use during lactation
Since there is no information regarding the continued use of trimetobenzamide during lactation, it is recommended to prioritize other medications, especially when breastfeeding newborns or premature infants. Occasional short-term use of trimetobenzamide to treat nausea and vomiting appears to be acceptable.
◉ Effects on breastfed infants
As of the revision date, no relevant published information was found.
◉ Effects on lactation and breast milk
As of the revision date, no relevant published information was found.

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

Trimethobenzamide is an amide formed by the condensation of 3,4,5-trihydroxybenzoic acid and 4-[2-(N,N-dimethylamino)ethoxy]benzylamine. It is used to prevent nausea and vomiting in humans and has an antiemetic effect. It is a tertiary amine compound belonging to the benzamide class. Trimethobenzamide is a novel antiemetic that prevents nausea and vomiting in humans. Its mechanism of action is not yet clear, but it is likely related to the chemoreceptor trigger zone (CTZ). In dogs pretreated with Trimethobenzamide hydrochloride, apomorphine-induced vomiting was suppressed, but there was little protection against vomiting induced by intragastric administration of copper sulfate. Trimethobenzamide is an antiemetic. Trimetobenzamide's physiological action is achieved by inhibiting vomiting. Trimetobenzamide is an oral antiemetic used to treat nausea and vomiting caused by drugs, gastrointestinal disorders, viral infections, and other illnesses. There is no conclusive evidence that trimetobenzamide is associated with elevated serum enzymes during treatment. Despite its widespread use for nearly 50 years, it has rarely been found to be associated with clinically significant liver damage and jaundice.
See also: Trimetobenzamide hydrochloride (salt form).
Drug Indications
For the treatment of postoperative nausea and vomiting and nausea caused by gastroenteritis.
FDA Label
Mechanism of Action
The mechanism of action of trimetobenzamide, as determined in animal studies, is unclear, but may involve the chemoreceptor trigger zone (CTZ), the area in the medulla oblongata that transmits vomiting impulses; impulses directly stimulating the vomiting center do not appear to be similarly inhibited.
Drug…has been shown to inhibit stimulation of the chemoreceptor trigger zone in animals…/hydrochloride/
Therapeutic Use
Antiemetic
When administered subcutaneously, its antiemetic potency is approximately one-tenth that of chlorpromazine; when administered orally, it is approximately one-quarter that of chlorpromazine. /hydrochloride/
…It has little value in the prevention and treatment of motion sickness. /Hydrochloride/
Studies of trichomoniasis hydrochloride suppositories for the treatment of nausea and vomiting in children. Results showed that the drug was not superior to placebo in treating vomiting caused by gastritis; patients receiving nausea treatment reported symptom relief.
Drug (Veterinary): Antiemetic/Hydrochloride/

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Drug Warnings
Central nervous system reactions such as opisthotonus, seizures, coma, and extrapyramidal symptoms may occur in patients with acute fever, illness, encephalitis, gastroenteritis, dehydration, and electrolyte imbalance (especially in children, the elderly, and the debilitated)...but it cannot be determined that all these effects are caused by the drug in all cases. Hydrochloride/
...Caution should be exercised when using trichomoniasis hydrochloride.../For patients with acute febrile illness, encephalitis, gastroenteritis, dehydration, and electrolyte imbalance (especially in children, the elderly, and the debilitated). /Hydrochloride/
Injection is contraindicated in children; suppositories are contraindicated in premature infants or newborns; and patients with known hypersensitivity to this product are contraindicated. Furthermore, suppositories are contraindicated in patients with known hypersensitivity to benzocaine or similar topical medications. Anesthetics. /Hydrochloride/
Caution should be exercised when using all antiemetics, as they may mask symptoms of organic diseases (such as gastrointestinal or central nervous system disorders) or the toxic effects of other drugs. …Personnel requiring vigilance…should use antiemetics with extreme caution. /Antiemetics/

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Pharmacodynamics
Tripetrombinamide is a novel antiemetic used to prevent nausea and vomiting in humans. Its mechanism of action is not fully understood, but it is likely related to the chemoreceptor trigger zone (CTZ). In dogs pretreated with trimetrombin hydrochloride, apomorphine-induced vomiting was suppressed, but there was little protection against vomiting induced by intragastric administration of 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

69.26

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

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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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。