甲氧氯普胺 (0.01-10 μM) 刺激离体大鼠肾小球带灌注细胞中醛固酮的释放 [3]。乙酰胆碱 (ACh) 通过甲氧氯普胺引起的四种机制从内在胆碱能运动神经元中释放：抑制突触前 D2 受体、刺激突触前兴奋性 5-HT4 受体、抑制 D2 突触后受体以及拮抗毒蕈碱受体的突触前抑制，从而导致进一步增加乙酰胆碱的释放[2]。

在整个动情周期中，甲氧氯普胺（6.7 µg/g；每日皮下注射，持续 50 天）可显着提高垂体催乳素细胞的体积和数量 [4]。腹腔内用甲氧氯普胺（5-40 mg/kg）治疗的小鼠表现出僵直症，并且不太可能响应阿扑吗啡而爬上笼子[5]。腹腔注射甲氧氯普胺（1.25-2.5 mg/kg）的小鼠可能会表现出爬笼子的典型行为[5]。

Animal/Disease Models: Adult female mice of Swiss EPM-1 strain [4]
Doses: 6.7 µg/g
Route of Administration: daily subcutaneous injection for 50 days
Experimental Results: Increased the amount of prolactin and also stimulated its metabolic activity.

Absorption, Distribution and Excretion
Metoclopramide is rapidly absorbed in the gastrointestinal tract with an absorption rate of about 84%. The bioavailability of the oral preparation is reported to be about 40.7%, but can range from 30-100%. Nasal metoclopramide is 47% bioavailable. A 15mg dose reaches a Cmax of 41.0 ng/mL, with a Tmax of 1.25 h, and an AUC of 367 ng\*h/mL.
About 85% of an orally administered dose was measured in the urine within 72 hours during a pharmacokinetic study. An average of 18% to 22% of 10-20 mg dose was recovered as free drug within 3 days of administration.
The volume of distribution of metoclopramide is approximately 3.5 L/kg. This implies a high level of tissue distribution. Metoclopramide crosses the placental barrier and can cause extrapyramidal symptoms in the fetus.
The renal clearance of metoclopramide is 0.16 L/h/kg with a total clearance of 0.7 L/h/kg. Clinical studies showed that the clearance of metoclopramide may be reduced by up to 50% in patients with renal impairment. After high intravenous doses, total metoclopramide clearance ranged from 0.31 to 0.69 L/kg/h.
Metoclopramide is rapidly and almost completely absorbed from the GI tract following oral administration; however, absorption may be delayed or diminished in patients with gastric stasis. Considerable interindividual variations (up to fivefold) in peak plasma concentration have been reported with the same oral dose of metoclopramide. This variability apparently results from interindividual differences in first-pass metabolism of the drug.
Bioavailability of metoclopramide appears to correlate with the ratio of free:conjugated metoclopramide concentrations in urine. It appears that sulfate conjugation in the GI lumen and/or during first pass through the liver is the principal determinant of bioavailability of orally administered metoclopramide. The absolute bioavailability of orally administered metoclopramide has not been clearly established in humans, but limited data indicate that 30-100% of an oral dose of the drug reaches systemic circulation as unchanged metoclopramide. Following IM administration, the absolute bioavailability of metoclopramide is 74-96%.
Following oral administration of a single 10-mg dose of the drug in healthy, fasting adults in one study, peak plasma metoclopramide concentrations of 32-44 ng/mL occurred at 1-2 hours; following oral administration of a single 20-mg dose, peak plasma metoclopramide concentrations of 72-87 ng/mL occurred at an average of 2 hours.
In a study in infants (3.5 weeks-5.4 months of age) with gastroesophageal reflux who received 0.15-mg/kg oral doses of metoclopramide every 6 hours for 10 doses as an oral solution, the mean peak plasma concentration (56.8 ng/mL) of the drug after the 10th dose was twofold higher compared with that after the first dose (29 ng/mL), suggesting that metoclopramide accumulates in plasma following multiple oral dosing in this age group. In these patients, time to reach mean peak plasma concentrations (2.2 hours) was similar after the 10th dose to that occurring after the first dose.
For more Absorption, Distribution and Excretion (Complete) data for Metoclopramide (18 total), please visit the HSDB record page.

---

Metabolism / Metabolites
Metoclopramide undergoes first-pass metabolism and its metabolism varies according to the individual. This drug is metabolized by cytochrome P450 enzymes in the liver. CYP2D6 and CYP3A4 both contribute to its metabolism, with CYP2D6 being more heavily involved. CYP1A2 is also a minor contributing enzyme. The process of N-4 sulphate conjugation is a primary metabolic pathway of metoclopramide.
Although the exact metabolic fate of metoclopramide is not clearly established, it appears that metoclopramide is only minimally metabolized. The major metabolite found in urine is 2-[(4-amino-5-chloro-2-methoxybenzoyl)amino]acetic acid; it is not known if this metabolite is pharmacologically active. Metoclopramide is conjugated with sulfuric and/or glucuronic acid.
Metoclopramide has known human metabolites that include monodeethylmetoclopramide.

---

Biological Half-Life
The mean elimination half-life of metoclopramide in people with healthy renal function ranges from 5 to 6 hours but is prolonged in patients with renal impairment. Downward dose adjustment should be considered.
In adults, the half-life of metoclopramide in the initial phase (t1/2 alpha) is about 5 minutes, and the half-life in the terminal phase (t1/2 beta) ranges from 2.5-6 hours. In children receiving oral or IV metoclopramide, the elimination half-life of the drug reportedly is 4.1-4.5 hours. Following oral administration of 0.15-mg/kg doses of metoclopramide every 6 hours for 10 doses in an infant (3.5 weeks of age), elimination half-lives of 23.1 and 10.3 hours were observed after the first and 10th dose, respectively, which were substantially longer than those reported in older infants, suggesting a reduced clearance in the neonate possibly being associated with immature renal and hepatic functions present at birth.

Interactions
The effects of metoclopramide on gastrointestinal motility are antagonized by anticholinergic drugs and narcotic analgesics. Additive sedative effects can occur when metoclopramide is given with alcohol, sedatives, hypnotics, narcotics, or tranquilizers.
The finding that metoclopramide releases catecholamines in patients with essential hypertension suggests that it should be used cautiously, if at all, in patients receiving monoamine oxidase inhibitors.
Absorption of drugs from the stomach may be diminished (e.g., digoxin) by metoclopramide, whereas the rate and/or extent of absorption of drugs from the small bowel may be increased (e.g., acetaminophen, tetracycline, levodopa, ethanol, cyclosporine).
Gastroparesis (gastric stasis) may be responsible for poor diabetic control in some patients. Exogenously administered insulin may begin to act before food has left the stomach and lead to hypoglycemia. Because the action of metoclopramide will influence the delivery of food to the intestines and thus the rate of absorption, insulin dosage or timing of dosage may require adjustment.
For more Interactions (Complete) data for Metoclopramide (10 total), please visit the HSDB record page.

---

Non-Human Toxicity Values
LD50 Rat oral 750 mg/kg
LD50 Rat ip 114 mg/kg
LD50 Rat sc 340 mg/kg
LD50 Rat iv 50 mg/kg
For more Non-Human Toxicity Values (Complete) data for Metoclopramide (8 total), please visit the HSDB record page.

[1]. Synthesis and structure-activity relationships of 4-amino-5-chloro-N-(1,4-dialkylhexahydro-1,4-diazepin-6-yl)-2-methoxybenzamide derivatives, novel and potent serotonin 5-HT3 and dopamine D2 receptors dual antagonist. Chem Pharm Bull (.

[2]. Review article: metoclopramide and tardive dyskinesia. Aliment Pharmacol Ther. 2010 Jan;31(1):11-9.

[3]. In vivo and in vitro studies on the effect of metoclopramide on aldosterone secretion. Clin Endocrinol (Oxf). 1980 Jul;13(1):45-50.

[4]. Dose-dependent response of central dopaminergic systems to metoclopramide in mice. Indian J Exp Biol. 1997 Jun;35(6):618-22.

[5]. Effects of metoclopramide on the mouse anterior pituitary during the estrous cycle. Clinics (Sao Paulo). 2011;66(6):1101-4.

Therapeutic Uses
Antiemetics; Dopamine Antagonists
Metoclopramide tablets are indicated as short-term (4 to 12 weeks) therapy for adults with symptomatic, documented gastroesophageal reflux who fail to respond to conventional therapy. /Included in US product label/
Metoclopramide tablets, USP is indicated for the relief of symptoms associated with acute and recurrent diabetic gastric stasis. The usual manifestations of delayed gastric emptying (eg, nausea, vomiting, heartburn, persistent fullness after meals, and anorexia) appear to respond to Metoclopramide Tablets within different time intervals. Significant relief of nausea occurs early and continues to improve over a three-week period. Relief of vomiting and anorexia may precede the relief of abdominal fullness by one week or more. /Included in US product label/
Metoclopramide injection is indicated for the prophylaxis of vomiting associated with emetogenic cancer chemotherapy. /Included in US product label/
For more Therapeutic Uses (Complete) data for Metoclopramide (8 total), please visit the HSDB record page.

---

Drug Warnings
WARNING: TARDIVE DYSKINESIA-Treatment with metoclopramide can cause tardive dyskinesia, a serious movement disorder that is often irreversible. The risk of developing tardive dyskinesia increases with duration of treatment and total cumulative dose. Metoclopramide therapy should be discontinued in patients who develop signs or symptoms of tardive dyskinesia. There is no known treatment for tardive dyskinesia. In some patients, symptoms may lessen or resolve after metoclopramide treatment is stopped. Treatment with metoclopramide for longer than 12 weeks should be avoided in all but rare cases where therapeutic benefit is thought to outweigh the risk of developing tardive dyskinesia.
Adverse reactions to metoclopramide generally involve the CNS and GI tract and are usually mild, transient, and reversible following discontinuance of the drug. In general, the incidence of metoclopramide-induced adverse effects is related to dosage and duration of therapy.
The most frequent adverse effects of metoclopramide involve the CNS. Restlessness, drowsiness, fatigue, and lassitude have been reported in patients receiving the drug; these effects occur in about 10% of patients receiving a dosage of 10 mg 4 times daily. Insomnia, headache, confusion, dizziness, or depression with suicidal ideation occurs less frequently. The risk of drowsiness is increased at higher doses, occurring in about 70% of patients receiving doses of 1-2 mg/kg. Seizures have been reported rarely, although a causal relationship to metoclopramide has not been established. Hallucinations also have been reported rarely. Feelings of anxiety or agitation also may occur, especially following rapid IV injection of the drug.
Extrapyramidal reactions (eg, acute dystonic reactions, akathisia) may occur in patients receiving metoclopramide and apparently are mediated via blockade of central dopaminergic receptors involved in motor function. Although extrapyramidal reactions may occur in all age groups and at any dose, they occur more frequently in pediatric patients and adults younger than 30 years of age and following IV administration of high doses of the drug (eg, those used in prophylaxis of cancer chemotherapy-induced vomiting). Extrapyramidal reactions generally occur within 24-48 hours after starting therapy and usually subside within 24 hours following discontinuance of the drug.
For more Drug Warnings (Complete) data for Metoclopramide (31 total), please visit the HSDB record page.

---

Pharmacodynamics
Metoclopramide increases gastric emptying by decreasing lower esophageal sphincter (LES) pressure. It also exerts effects on the area postrema of the brain, preventing and relieving the symptoms of nausea and vomiting. In addition, this drug increases gastrointestinal motility without increasing biliary, gastric, or pancreatic secretions. Because of its antidopaminergic activity, metoclopramide can cause symptoms of tardive dyskinesia (TD), dystonia, and akathisia, and should therefore not be administered for longer than 12 weeks.

C14H22CLN3O2

299.7964

299.14

364-62-5

Metoclopramide hydrochloride hydrate;54143-57-6;Metoclopramide hydrochloride;7232-21-5

4168

White to off-white solid powder

1.2±0.1 g/cm3

454.8±55.0 °C at 760 mmHg

146-148°C

228.9±31.5 °C

0.0±1.2 mmHg at 25°C

1.545

3.1

67.59

2

4

7

20

300

0

TTWJBBZEZQICBI-UHFFFAOYSA-N

InChI=1S/C14H22ClN3O2/c1-4-18(5-2)7-6-17-14(19)10-8-11(15)12(16)9-13(10)20-3/h8-9H,4-7,16H2,1-3H3,(H,17,19)

4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxybenzamide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 本产品在运输和储存过程中需避光。

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

DMSO : ~110 mg/mL (~366.91 mM)

配方 1 中的溶解度: ≥ 2.75 mg/mL (9.17 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 27.5 mg/mL澄清DMSO储备液加入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: ≥ 2.75 mg/mL (9.17 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 27.5 mg/mL 澄清 DMSO 储备液加入900 μL 玉米油中，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。