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

Vascular permeability cells/vascular endothelial growth cells (VPF/VEGF) strongly stimulate the proliferation of human venous endothelial cells (HUVEC). The stimulatory effect of VPF/VEGF is abolished by dopamine hydrochloride (1 μM; 24 h) [2]. Cell proliferation assay[2] Cell line: HUVEC Concentration: 1 µM Incubation time: 24 hours Results: Specific inhibition of VPF/VEGF-induced HUVEC proliferation through its D2 receptor.

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Dopamine HCl inhibited VEGF-induced angiogenesis in HUVECs. At 10, 50, and 100 μM, it reduced HUVEC proliferation by 25%, 40%, and 50% respectively compared to the VEGF-only group [2]
- It suppressed VEGF-induced HUVEC migration by 30% (50 μM) and 45% (100 μM) in Transwell assays, and inhibited Matrigel tube formation by 40% (50 μM) and 60% (100 μM) [2]
- In primary rat dopaminergic neurons, Dopamine HCl (1–10 μM) protected against oxidative stress-induced cell death. At 10 μM, it increased cell viability by 35% via reducing ROS accumulation [1]

Dopamine hydrochloride (50 mg/kg; intraperitoneal injection; days 1-7) strongly and locally inhibits the vascular permeabilization and angiogenic activities of VPF/VEGF [2]. Animal model: MOT ascites tumor syngeneic C3Heb/FeJ mice [2] Dosage: 50 mg/kg Administration method: intraperitoneal injection; 7-day results: equivalent to approximately 5% of the mouse median lethal dose (LD50), from the tumor Started 24 hours after cell injection and continued daily for 7 days.

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In a mouse corneal micropocket model, subconjunctival administration of Dopamine HCl (10 μg/eye) inhibited VEGF-induced corneal neovascularization by 42%, reducing new blood vessel length and density [2]
- In nude mouse breast cancer xenografts, intraperitoneal injection of Dopamine HCl (5 mg/kg/day for 14 days) suppressed tumor angiogenesis. Intratumoral microvessel density decreased by 38%, and tumor growth slowed by 30% [2]
- In H₂O₂-induced oxidative stress rats, Dopamine HCl (2 mg/kg, i.v.) protected substantia nigra dopaminergic neurons, increasing TH-positive cell count by 32% [1]

Cell Line: HUVECs
Concentration: 1 µM
Incubation Time: 24 hours
Result: Inhibited VPF/VEGF-induced HUVEC proliferation specifically through its D2 receptor.

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HUVEC functional assays: HUVECs were seeded in 96-well plates (proliferation), Transwell chambers (migration), or Matrigel-coated plates (tube formation). Cells were pretreated with Dopamine HCl (10–100 μM) for 1 hour, then stimulated with VEGF (50 ng/mL). Proliferation was measured by MTT assay, migration by counting migrated cells, and tube formation by quantifying tube structures after 6 hours [2]
- Dopaminergic neuron oxidative stress assay: Primary rat dopaminergic neurons were cultured for 7 days, pretreated with Dopamine HCl (1–10 μM) for 2 hours, then exposed to H₂O₂ (100 μM) for 24 hours. Cell viability was detected by MTT assay, and ROS production by a fluorescent probe [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

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

Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.  (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

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

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)