Microbial Metabolite; D2 Dopamine Receptor
Dopamine receptors (D1-D5 subtypes) [1][2]

血管通透性细胞/血管内皮生长细胞 (VPF/VEGF) 强烈刺激人静脉内皮细胞 (HUVEC) 增殖。VPF/VEGF 的刺激作用被盐酸多巴胺 (1 μM；24 h) 消除[2]。 细胞增殖测定[2] 细胞系：HUVEC 浓度：1 µM 孵育时间：24 小时 结果：通过其 D2 受体特异性抑制 VPF/VEGF 诱导的 HUVEC 增殖。

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Dopamine HCl（盐酸多巴胺） 抑制VEGF诱导的人脐静脉内皮细胞（HUVECs）血管生成。10、50、100 μM浓度下，较单纯VEGF组分别减少25%、40%和50%的HUVEC增殖[2]
- 该化合物在Transwell迁移实验中，50 μM浓度抑制30%、100 μM抑制45%的VEGF诱导HUVEC迁移；Matrigel管腔形成实验中，50 μM抑制40%、100 μM抑制60%的管腔形成[2]
- 在原代大鼠多巴胺能神经元中，Dopamine HCl（1–10 μM）保护细胞免受氧化应激诱导的死亡，10 μM时通过减少活性氧（ROS）积累提高35%的细胞活力[1]

盐酸多巴胺（50 mg/kg；腹腔注射；1-7天）强烈且定位地抑制VPF/VEGF的血管透化和血管生成活性[2]。动物模型：MOT腹水肿瘤同基因C3Heb/FeJ小鼠[ 2]剂量：50 mg/kg 给药方式：腹腔注射； 7 天结果：相当于小鼠半数致死剂量 (LD50) 的约 5%，从肿瘤细胞注射后 24 小时开始，每天持续，持续 7 天。

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在小鼠角膜微囊血管生成模型中，结膜下注射Dopamine HCl（10 μg/眼）抑制42%的VEGF诱导角膜新生血管，减少新生血管长度和密度[2]
- 在裸鼠人乳腺癌异种移植模型中，腹腔注射Dopamine HCl（5 mg/kg/天，连续14天）抑制肿瘤血管生成，肿瘤内微血管密度降低38%，肿瘤生长速度减慢30%[2]
- 在过氧化氢（H₂O₂）诱导的氧化应激大鼠中，Dopamine HCl（2 mg/kg，静脉注射）保护黑质多巴胺能神经元，酪氨酸羟化酶（TH）阳性细胞数增加32%[1]

细胞系：HUVEC
浓度：1 µM
孵育时间：24 小时
结果：通过其 D2 受体特异性抑制 VPF/VEGF 诱导的 HUVEC 增殖。

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HUVEC功能实验：HUVEC分别接种于96孔板（增殖）、Transwell小室（迁移）或Matrigel包被板（管腔形成）。Dopamine HCl（10–100 μM）预处理1小时后，加入VEGF（50 ng/mL）刺激。MTT法检测增殖，计数迁移细胞评估迁移能力，6小时后定量管腔结构[2]
- 多巴胺能神经元氧化应激实验：原代大鼠多巴胺能神经元培养7天，Dopamine HCl（1–10 μM）预处理2小时后，暴露于H₂O₂（100 μM）24小时。MTT法检测细胞活力，荧光探针检测ROS产生[1]

Syngeneic C3Heb/FeJ mice with MOT ascites tumors
50 mg/kg
I.p. injection; 7 days

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Mouse corneal angiogenesis model: C57BL/6 mice were anesthetized, a corneal micropocket was created, and a VEGF-soaked pellet was implanted. Dopamine HCl (10 μg/eye) or saline was administered subconjunctivally. After 7 days, corneas were stained with FITC-dextran, and new blood vessel length/density were measured [2]
- Nude mouse tumor xenograft model: Human breast cancer cells were subcutaneously implanted into nude mice. When tumors reached 100 mm³, Dopamine HCl (5 mg/kg/day, i.p.) or saline was given for 14 days. Tumor volume was measured every 2 days, and intratumoral microvessel density was analyzed by CD31 immunohistochemistry [2]

Absorption, Distribution and Excretion
Dopamine is rapidly absorbed in the small intestine.
It has been reported that approximately 80% of the drug is excreted in the urine within 24 hours, primarily as homovanillic acid (HVA) and its sulfate and glucuronide conjugates, as well as 3,4-dihydroxyphenylacetic acid. A very small amount is excreted unchanged.
Dopamine is commonly used to treat shock and heart failure in critically ill newborns, but its pharmacokinetics have not been evaluated using specific analytical methods. This study measured the steady-state arterial plasma dopamine concentrations in 11 critically ill infants with suspected or confirmed sepsis and hypotensive shock after treatment with dopamine infusions (5-20 μg/kg⁻¹·min⁻¹). The steady-state dopamine concentration ranged from 0.013 to 0.3 μg/mL. The mean systemic clearance was 115 mL/kg⁻¹·min⁻¹. The apparent volume of distribution and elimination half-life were 1.8 L/kg⁻¹ and 6.9 min, respectively. No correlation was observed between dopamine pharmacokinetics and gestational age, postnatal age, or birth weight. Significant inter-individual variability in dopamine pharmacokinetics exists in critically ill infants, and plasma concentrations cannot be accurately predicted based on infusion rate. The significant variability in clearance partially explains the wide range of dopamine doses required to achieve clinical efficacy in critically ill neonates. Less than 10% of the dose is excreted unchanged in the urine. Plasma dopamine concentrations at steady state or at the end of infusion were determined by high-performance liquid chromatography (HPLC) in children (3 months to 13 years) recovering from cardiac surgery or shock. The distribution half-life and elimination half-life of dopamine were 1.8 ± 1.1 min and 26 ± 14 (SD) min, respectively. The apparent volume of distribution was 2952 ± 2332 mL/kg. The clearance was 454 ± 900 mL/kg·min. In patients receiving dobutamine concomitantly, dopamine clearance was linearly related to dose (r² = 0.76, p < 0.05). Hepatic and renal dysfunction did not affect the pharmacokinetics of dopamine. Interactions between dopamine and dobutamine may exist, affecting the distribution of both drugs in vivo. Individual differences in dopamine pharmacokinetics exist even in hemodynamically stable children. Hepatic and renal function did not affect the pharmacokinetics of dopamine. The brain contains an independent nervous system utilizing three different catecholamines—dopamine, norepinephrine, and epinephrine… More than half of the catecholamines in the central nervous system are dopamine, with extremely high concentrations in specific areas such as the basal ganglia (especially the caudate nucleus), nucleus accumbens, olfactory tubercle, central amygdala, median eminence, and frontal cortex. Dopamine is widely distributed throughout the body but has difficulty crossing the blood-brain barrier. The apparent volume of distribution of this drug in newborns is 0.6–4 L/kg. It is unclear whether dopamine can cross the placenta.

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Metabolism/Metabolites
Dopamine undergoes rapid biotransformation, with the main excretory products being 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylacetic acid (hovanillic acid, HVA).
Dopamine is extensively metabolized in the liver. …Hepatic metabolism produces inactive metabolites (75% of the dose) and norepinephrine (active, 25% of the dose), which reaches adrenergic nerve endings. The main elimination pathway appears to be O-methylation catalyzed by catechol-O-methyltransferase to produce 3-methoxytyramine, which is subsequently converted to homovanillic acid via sulfonation (catalyzed by benzylsulfonase) or deamination (catalyzed by monoamine oxidase (MAO)). Approximately 80% of the drug is excreted in the urine within 24 hours as homovanillic acid, homovanillic acid metabolites, and norepinephrine metabolites.
N-acetyl-3,4-dihydroxyphenylethylamine was produced in humans and rats; Hauson A, Studnitz W Von; Clinica Chim Acta 11: 384 (1965); Goldstein M, Musacchio Jm; Biochim Biophys Acta 58: 607 (1962). 3,4-dihydroxy-N-methylphenylethylamine was produced in rats; Laduron P; Nature New Biology 238: 212 (1972). /Excerpt from Table/
Production of 3,4-dihydroxyphenylethylamine-O-β-D-glucuronide in rats; Young Ja, Edwards Kdg; J Pharmac Exp Ther 145: 102 (1964). Production of 3,4-dihydroxyphenylacetaldehyde in humans and rats; Nagatsu T et al.; Enzymologia 39: 15 (1970); Goldstein M et al.; Biochim Biophys Acta 33: 572 (1959). /Excerpt from Table/
Production of 4-hydroxyphenylethylamine-3-ylsulfate in rats; Jenner Wn, Rose Fa; Biochem J 135: 109 (1973). Production of 3-methoxytyramine in humans; Goodall MCC, Alton A; Biochem Pharmac 17: 905 (1968). In humans, it produces d-norepinephrine; Sjoerdsma AJ et al.; J Clin Invest 38: 31 (1959). /Excerpt from Table/
For more complete data on the metabolism/metabolites of dopamine (a total of 8 metabolites), please visit the HSDB records page.
Known human metabolites of dopamine include dopamine 3-O-sulfate and dopamine 4-D-glucuronide.
Dopamine is a known human metabolite of tyramine.
Dopamine is rapidly biotransformed, with the main excretion products being 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylacetic acid (hovanillic acid, HVA).
Excretion pathway: Approximately 80% of the drug is reportedly excreted in the urine within 24 hours, primarily as HVA and its sulfate and glucuronide conjugates, as well as 3,4-dihydroxyphenylacetic acid.
Very small amounts of the drug are excreted via other routes. Unchanged.
Half-life: 2 minutes
Bio-half-life
2 minutes
Plasma dopamine concentrations in children (3 months to 13 years old) recovering from cardiac surgery or shock were determined by high-performance liquid chromatography (HPLC) at steady state or at the end of infusion. The distribution half-life and elimination half-life were 1.8 ± 1.1 minutes and 26 ± 14 (SD) minutes, respectively.
The plasma half-life of dopamine is approximately 2 minutes. The elimination half-life of dopamine in neonates has been reported to be 5–11 minutes.

Toxicity Summary
Dopamine is a precursor to norepinephrine in noradrenergic neurons and a neurotransmitter in certain areas of the central nervous system. Dopamine has positive chronotropic and positive inotropic effects on the myocardium, leading to increased heart rate and myocardial contractility. This is achieved through direct stimulation of β-adrenergic receptors and indirect stimulation of norepinephrine release from sympathetic nerve endings. In the brain, dopamine acts as an agonist of five dopamine receptor subtypes (D1, D2, D3, D4, and D5). Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
There is currently no information regarding the use of dopamine during lactation. Due to its low oral bioavailability and short half-life, dopamine in breast milk is unlikely to affect the infant. Intravenous infusion of dopamine may reduce milk production. Dopamine is known to lower serum prolactin levels in non-lactating women, but there is no information on its effects on milk production in lactating women.
◉ Effects on breastfed infants
As of the revision date, no relevant published information was found.
◉ Effects on lactation and breast milk
Intravenous infusion of dopamine at doses of 2 to 5 mcg/kg/min lowers serum prolactin concentrations in non-lactating women and women with hyperprolactinemia. However, as of the revision date, no relevant published information was found on the effects of intravenous dopamine infusion on milk production in lactating women. For mothers who have established lactation, prolactin levels may not affect their ability to breastfeed.
Protein binding
Currently, there is no information on protein binding.

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Toxicity Data
Oral LD50 in mice = 1460 mg/kg, oral LD50 in rats = 1780 mg/kg
Interactions
Inhibition of monoamine oxidase by furazolidone… If taken concurrently with other amine releasers/dopamine, patients may be at potential risk of hypertensive crisis.
…Patients currently taking or recently taking guanethidine may experience enhanced pharmacological responses to phenylephrine and other primarily direct-acting α-adrenergic sympathomimetic amines (e.g., dopamine…).
Effects on brain dopamine: In metabolic studies in rats, chlorpromazine, thioridazine, and thiamethoxam dose-dependently increased the concentration of 3,4-dihydroxyphenylacetic acid in the brain, and this concentration was associated with antipsychotic efficacy.
…Administration of depranidone inhibits the metabolic degradation of dopamine in the brain. For more complete data on dopamine interactions (12 in total), please visit the HSDB record page.

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Non-human toxicity values
Rat intraperitoneal LD50: 163 mg/kg
Mouse intraperitoneal LD50: 950 mg/kg
Mouse intravenous LD50: 59 mg/kg
Mouse intrajary LD50: 74 mg/kg
Dog intravenous LD50: 79 mg/kg

[1]. The Role of Dopamine and Its Dysfunction as a Consequence of Oxidative Stress. Oxid Med Cell Longev. 2016;2016:9730467.

[2]. The neurotransmitter dopamine inhibits angiogenesis induced by vascular permeability factor/vascular endothelial growth factor. Nat Med. 2001 May;7(5):569-74.

Therapeutic Uses
Inotropic Agents During cardiopulmonary resuscitation (CPR), dopamine is also used in advanced cardiovascular life support (ACLS) to increase cardiac output and blood pressure. For symptomatic bradycardia unresponsive to atropine, dopamine may be considered as a temporary measure, such as while waiting for a pacemaker to become available or when pacing is ineffective. During resuscitation, dopamine therapy is commonly used to control hypotension, especially in cases of symptomatic bradycardia or after the restoration of spontaneous circulation. Dopamine in combination with other drugs (such as dobutamine) may also be an effective treatment option for post-resuscitation hypotension. If hypotension persists after filling pressure (i.e., intravascular volume) optimization, drugs with positive inotropic and vasopressor effects (such as epinephrine, noradrenaline) may be used. Some evidence from animal studies suggests that epinephrine may be more effective than dopamine in improving hemodynamics during CPR. Furthermore, for patients with severe bradycardia and hypotension, epinephrine is generally the first choice because pulseless electrical activity or even cardiac arrest may be imminent. /US Product Label Content/
Dopamine's net hemodynamic effects make it particularly effective in treating cardiogenic shock (including shock associated with acute myocardial infarction) or oliguric shock unresponsive to other vasopressors. Some experts note that dopamine can be used to treat drug-induced hypovolemic shock, and it is often the recommended initial treatment when patients are unresponsive to fluid resuscitation and require support from positive inotropic and/or vasopressor drugs. In patients with left ventricular failure following acute myocardial infarction, if arterial blood pressure drops sharply during afterload reduction, dopamine can be used as an adjunct (to further increase cardiac output and maintain blood pressure) in combination with vasodilators (such as sodium nitroprusside); for smaller drops, dobutamine is preferred, but it should not be used alone in patients with severe hypotension. In patients with hypotensive cardiogenic shock following acute myocardial infarction, dopamine can be used as an alternative to norepinephrine once systemic arterial pressure rises to at least 80 mmHg. Once arterial blood pressure stabilizes at at least 90 mmHg, dobutamine and dopamine can be used in combination in these patients to reduce the required dose of dopamine. Dopamine has also been used to support cardiac output and maintain arterial blood pressure during intra-aortic balloon counterpulsation (IACP) therapy (e.g., in patients with hypotensive cardiogenic shock following acute myocardial infarction). Studies have shown that dopamine use in low cardiac output syndrome following open-heart surgery can improve long-term survival. However, because dobutamine reduces peripheral resistance over a wide dose range, its action is independent of the release of endogenous catecholamines, and it is cardiac selective, immediate use after cardiopulmonary bypass surgery may be more ideal. /US Product Label Content/
Dopamine is used to increase cardiac output, blood pressure, and urine output as an adjunct therapy for the treatment of shock that persists despite adequate fluid resuscitation and for conditions of decreased systemic vascular resistance. /Included in US Product Label/
For more complete data on the therapeutic uses of dopamine (12 types), please visit the HSDB record page.

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Drug Warnings
Dopamine should be used with caution in patients with ischemic heart disease. This drug is contraindicated in patients with pheochromocytoma, uncorrected tachyarrhythmias, or ventricular fibrillation.
Commercially available dopamine hydrochloride preparations may contain sulfites, and allergic reactions may occur in certain susceptible individuals, including anaphylactic shock and life-threatening or mild asthma attacks. The overall prevalence of sulfite allergy in the general population is unknown but is likely low; this allergy appears to be more common in asthmatic patients than in non-asthmatic patients.
Extravasation should be avoided. Dopamine should be administered via a long intravenous catheter into a larger vein, preferably the cubital fossa vein rather than the hand or ankle. One manufacturer notes that administration via the umbilical artery catheter is not recommended. If a larger vein is not available and the patient's condition necessitates administration via a hand or ankle vein, the injection site should be changed to a larger vein as soon as possible. The injection site should be closely monitored.
Patients with a history of occlusive vascular disease (e.g., atherosclerosis, arterial embolism, Raynaud's disease, frostbite, diabetic endarteritis, or thromboangiitis obliterans) should be closely monitored for decreased limb circulation, manifested as changes in skin color or temperature, or limb pain, during dopamine treatment. If these occur, they can be corrected by reducing the infusion rate or discontinuing dopamine. However, these changes can sometimes persist and worsen after discontinuation of dopamine. The potential benefits of continuing dopamine use should be weighed against the potential risk of necrosis.
For more complete data on dopamine (13 in total), please visit the HSDB record page.

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Pharmacodynamics
Dopamine is a natural catecholamine formed by the decarboxylation of 3,4-dihydroxyphenylalanine (DOPA). It is a precursor of norepinephrine in noradrenergic nerves and a neurotransmitter in certain areas of the central nervous system (especially the substantia nigra striatum) and a few peripheral sympathetic nerves. Dopamine has positive chronotropic and positive inotropic effects on the myocardium, thereby increasing heart rate and myocardial contractility. Dopamine hydrochloride (Dpamine HCl) is an endogenous catecholamine that functions as a neurotransmitter in the central nervous system and as a hormone in the peripheral nervous system [1][2]. Its mechanisms of action include activating D1-D5 dopamine receptors to regulate neuronal signaling and inhibiting VEGF-mediated downstream pathways (e.g., PI3K/Akt) to inhibit angiogenesis [1][2]. Physiologically, it is essential for motor control, reward, cognition, and vascular homeostasis [1]. Dysfunction of dopamine signaling is associated with oxidative stress-related neurodegenerative diseases such as Parkinson's disease [1].

C8H12CLNO2

189.64

189.055

C, 50.67; H, 6.38; Cl, 18.69; N, 7.39; O, 16.87

62-31-7

Dopamine; 51-61-6

681

White to off-white solid powder

337.7ºC at 760 mmHg

248-250 °C(lit.)

2.101

66.48

3

3

2

11

119

0

O([H])C1=C(C([H])=C([H])C(=C1[H])C([H])([H])C([H])([H])N([H])[H])O[H]

CTENFNNZBMHDDG-UHFFFAOYSA-N

InChI=1S/C8H11NO2.ClH/c9-4-3-6-1-2-7(10)8(11)5-6;/h1-2,5,10-11H,3-4,9H2;1H

4-(2-aminoethyl)benzene-1,2-diol;hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： (1). 本产品在运输和储存过程中需避光。  (2). 请将本产品存放在密封且受保护的环境中（例如氮气保护），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)

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：
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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；
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