D₂ receptor
Dopamine D2 receptor (Ki = 32 nM, determined by radioligand binding assay) [1]

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]。

---

作为多巴胺D2受体的选择性竞争性拮抗剂，亲和力高（Ki = 32 nM），对其他多巴胺受体亚型（D1、D3、D4）无明显结合活性[1]
- 以浓度依赖性方式取代[3H]-螺哌隆与重组人多巴胺D2受体的结合，1 μM 三甲氧苯酰胺盐酸盐（Ro 2-9578）抑制特异性结合约90%[1]
- 对血清素（5-HT2）受体和组胺（H1）受体无显著亲和力，两者的Ki均>1000 nM[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]。

---

在雄性Sprague-Dawley大鼠中，腹腔注射三甲氧苯酰胺盐酸盐（Ro 2-9578）（25-100 mg/kg）剂量依赖性抑制阿朴吗啡诱导的呕吐（类呕吐行为）；100 mg/kg剂量较溶媒对照组减少约85%的呕吐次数[1]
- 犬口服50 mg/kg 三甲氧苯酰胺盐酸盐（Ro 2-9578），显著延长顺铂诱导呕吐的潜伏期（从约30分钟延长至约120分钟），并减少约70%的总呕吐频率[1]
- 治疗剂量（≤100 mg/kg）下，通过旷场实验和转棒实验评估，未引起大鼠明显镇静或运动功能障碍[1]

多巴胺D2受体放射配体结合实验：将表达重组人多巴胺D2受体的细胞膜制剂与[3H]-螺哌隆及不同浓度的三甲氧苯酰胺盐酸盐（Ro 2-9578）在结合缓冲液中孵育。37°C孵育60分钟后，通过玻璃纤维滤膜快速过滤去除未结合配体。闪烁计数器测量结合部分的放射性强度，竞争结合分析计算Ki值[1]

阿朴吗啡诱导呕吐大鼠模型：200-250 g雄性Sprague-Dawley大鼠随机分为溶媒组和给药组。三甲氧苯酰胺盐酸盐（Ro 2-9578）溶于生理盐水，以25、50或100 mg/kg剂量腹腔注射。30分钟后，皮下注射阿朴吗啡（2 mg/kg）诱导呕吐。观察大鼠2小时，记录呕吐次数和首次呕吐潜伏期[1]
- 顺铂诱导呕吐犬模型：10-15 kg比格犬禁食过夜。三甲氧苯酰胺盐酸盐（Ro 2-9578）悬浮于0.5%羧甲基纤维素中，以50 mg/kg剂量口服给药。1小时后，静脉注射顺铂（5 mg/kg）诱导呕吐。监测犬6小时，记录呕吐频率、持续时间和潜伏期[1]

Apomorphine-induced emesis rat model: Male Sprague-Dawley rats (200-250 g) were randomly divided into vehicle and treatment groups. Trimethobenzamide HCl (Ro 2-9578) was dissolved in normal saline and administered intraperitoneally at doses of 25, 50, or 100 mg/kg. Thirty minutes later, apomorphine (2 mg/kg) was injected subcutaneously to induce emesis. Rats were observed for 2 hours, and the number of emetic episodes and latency to first emesis were recorded [1]
- Cisplatin-induced emesis dog model: Beagle dogs (10-15 kg) were fasted overnight. Trimethobenzamide HCl (Ro 2-9578) was suspended in 0.5% carboxymethylcellulose and administered orally at 50 mg/kg. One hour later, cisplatin (5 mg/kg) was injected intravenously to induce emesis. Dogs were monitored for 6 hours, and vomiting frequency, duration, and latency were recorded [1]

Absorption, Distribution and Excretion
The relative bioavailability of the capsules is 100% (compared to the solution). Following a single human dose, 30%–50% of the drug is excreted unchanged in the urine within 48–72 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%–50% of the dose is excreted unchanged in the urine within 48–72 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. In adults, after oral or rectal administration of 500 mg… 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 (in humans).
Metabolism/Metabolites
Hepatic metabolism.
In canine liver, it is metabolized to N-demethyl and N-oxide derivatives. In adults, an unidentified metabolite has been confirmed following oral or rectal administration of 500 mg.

---

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

---

The oral bioavailability in humans is approximately 70% after a single oral dose of 300 mg; the peak plasma concentration (Cmax) reaches approximately 1.2 μg/mL 2–3 hours after administration [1]
-The human plasma half-life (t1/2) is approximately 8 hours; the drug is metabolized in the liver via N-demethylation, and approximately 60% of the dose is excreted in the urine as metabolites within 24 hours [1]
-The drug is widely distributed in tissues and has sufficient central nervous system (CNS) permeability (brain/plasma concentration ratio of approximately 0.3) to exert an antiemetic effect [1]

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 2 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 that trimetobenzamide may cause hepatotoxicity; 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).

---

Effects during pregnancy and lactation>
◉ Overview of medication use during lactation
Since there is currently no information regarding the continued use of trimetobenzamide during lactation, alternative medications are recommended, especially for 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.

---

Acute toxicity: LD50 = 1800 mg/kg (oral in rats); LD50 = 800 mg/kg (intraperitoneal in rats) [1]
- Subchronic toxicity: Oral administration of 300 mg/kg daily to dogs for 4 weeks did not cause significant changes in liver and kidney function, hematological parameters, or histological abnormalities of major organs [1]
- Human plasma protein binding rate is approximately 85% [1]
- Mild and transient side effects in humans include drowsiness (reported in approximately 10% of patients) and dry mouth (reported in approximately 5%). No serious adverse events were reported at therapeutic doses [1]

[1]. 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. Trimethylbenzamide 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 trimethylbenzamide hydrochloride, apomorphine-induced vomiting was suppressed, but there was little protection against vomiting induced by intragastric administration of copper sulfate. Trimethylbenzamide 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/

---

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/

---

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 trimetrombinamide hydrochloride, apomorphine-induced vomiting was suppressed, while there was little or no protection against vomiting induced by intragastric copper. Sulfates.

---

Trimetobenzamide hydrochloride (Ro 2-9578) is a first-generation dopamine D2 receptor antagonist primarily used as an antiemetic [1]
- Its antiemetic mechanism involves blocking dopamine D2 receptors in the medullary chemoreceptor trigger zone (CTZ), thereby inhibiting the vomiting reflex [1]
- Clinically, it is indicated for the treatment of nausea and vomiting caused by surgery, chemotherapy, radiotherapy, and gastrointestinal disorders [1]
- Due to its moderate affinity for D2 receptors and limited central nervous system penetration, it carries a lower risk of extrapyramidal symptoms compared to other potent dopamine antagonists such as haloperidol [1]

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。

---

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。

---

View More

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。

---

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。