Human umbilical vein endothelial cells (HUVEC) are highly stimulated to proliferate by vascular permeability factor/vascular endothelial growth factor (VPF/VEGF). One hour later, dopamine (1 µM) eliminates the stimulatory action of VPF/VEGF [2].

Dopamine (50 mg/kg; i.p.; days 1-7) strongly and selectively inhibits the vascular permeability and angiogenic activity of VPF/VEGF [2].

Cell proliferation assay[2]
Cell Types: HUVEC
Tested Concentrations: 1 µM
Incubation Duration: 24 hrs (hours)
Experimental Results: Specific inhibition of VPF/VEGF-induced HUVEC proliferation through its D2 receptor.

Animal/Disease Models: Syngeneic C3Heb/FeJ mice with MOT ascites tumors[2]
Doses: 50 mg/kg
Route of Administration: intraperitoneal (ip) injection; 7-day
Experimental Results: equivalent to approximately 5% of the median lethal dose (LD50) in mice , starting 24 hrs (hrs (hours)) after tumor cell injection and continuing daily for 7 days.

Absorption, Distribution and Excretion
Dopamine is rapidly absorbed from the small intestine.
It has been reported that about 80% of the drug is excreted in the urine within 24 hours, primarily as HVA and its sulfate and glucuronide conjugates and as 3,4-dihydroxyphenylacetic acid. A very small portion is excreted unchanged.
Dopamine is frequently used in critically ill newborn infants for treatment of shock and cardiac failure, but its pharmacokinetics has not been evaluated using a specific analytical method. Steady-state arterial plasma concentrations of dopamine were measured in 11 seriously ill infants receiving dopamine infusion, 5-20 ug/kg-1.min-1, for presumed or proven sepsis and hypotensive shock. Steady-state concentrations of dopamine ranged from 0.013-0.3 ug/mL. Total body clearance averaged 115 mL/kg-1.min-1. The apparent volume of distribution and elimination half life averaged 1.8 l.kg-1 and 6.9 min, respectively. No relationship was observed between dopamine pharmacokinetics and gestational age, postnatal age or birthweight. Substantial interindividual variation was seen in dopamine pharmacokinetics in seriously ill infants, and plasma concentrations could not be predicted accurately from its infusion rate. Marked variation in clearance explains in part, the wide dose requirements of dopamine needed to elicit clinical response in critically ill newborn infants.
Less than 10% of a dose is recovered unchanged in the urine.
Plasma dopamine concentrations /of children (age 3 months to 13 yrs) recovering from cardiac surgery or shock/ were measured at the steady state or at termination of infusion using high-performance liquid chromatography. The half-lives of distribution and elimination were 1.8 +/- 1.1 and 26 +/- 14 (SD) mins, respectively. The apparent volume of distribution was 2952 +/- 2332 mL/kg. The clearance rate was 454 +/- 900 mL/kg.min. Dopamine clearance was linearly related to dose only in patients who were also receiving dobutamine (r2 = .76, p less than .05). Hepatic and renal dysfunction did not affect the pharmacokinetics of dopamine. A relationship between dopamine and dobutamine that affects the disposition of these two drugs may exist. The pharmacokinetics of dopamine are variable even in hemodynamically stable children. Hepatic or renal function does not adversely affect the pharmacokinetics of dopamine.
The brain contains separate neuronal systems that utilize 3 different catecholamines- dopamine, norepinephrine, and epinephrine ... More than half of the central nervous system content of catecholamine is dopamine and extremely high amt are found in the basal ganglia (especially the caudate nucleus), the nucleus accumbens, the olfactory tubercle, the central nucleus of the amygdala, the median eminence, and restricted fields of the frontal cortex.
Dopamine is widely distributed in the body but does not cross the blood-brain barrier to a substantial extent. The apparent volume of distribution of the drug in neonates ranges from 0.6-4 L/kg. It is not known if dopamine crosses the placenta.

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Metabolism / Metabolites
Biotransformation of dopamine proceeds rapidly to yield the principal excretion products, 3-4-dihydroxy-phenylacetic acid (DOPAC) and 3-methoxy-4-hydroxy-phenylacetic acid (homovanillic acid, HVA).
Dopamine is extensively metabolized in the liver. ... Hepatic metabolism results in inactive metabolites (75% of the dose) and norepinephrine (active, 25% of the dose) in the adrenergic nerve terminals. The principal means of elimination appear to be O-methylation by catechol-O-methyltransferase to form 3-methoxytyramine, followed either by sulfoconjugation (by phenosulfotransferase) or by deamination (by monoamine oxidase (MAO)) to homovanillic acid. Approximately 80% of the drug is excreted in the urine as homovanillic acid, homovanillic acid metabolites, and norepinephrine metabolites within 24 hours.
Yields N-acetyl-3,4-dihydroxyphenethylamine in man, in rat; Hauson A, Studnitz W Von; Clinica Chim Acta 11: 384 (1965); Goldstein M, Musacchio Jm; Biochim Biophys Acta 58: 607 (1962). Yields 3,4-dihydroxy-n-methylphenethylamine in rat; Laduron P; Nature New Biology 238: 212 (1972). /From table/
Yields 3,4-dihydroxyphenethylamine-o-beta-d-glucuronide in rat; Young Ja, Edwards Kdg; J Pharmac Exp Ther 145: 102 (1964). Yields 3,4-dihydroxyphenylacetaldehyde in man and rat; Nagatsu T et al; Enzymologia 39: 15 (1970); Goldstein M et al; Biochim Biophys Acta 33: 572 (1959). /From table/
Yields 4-hydroxyphenethyamin-3-yl sulfate in rat; Jenner Wn, Rose Fa; Biochem J 135: 109 (1973). Yields 3-methoxytyramine in man; Goodall MCC, Alton A; Biochem Pharmac 17: 905 (1968). Yields d-noradrenaline in man; Sjoerdsma AJ et al; J Clin Invest 38: 31 (1959). /From table/
For more Metabolism/Metabolites (Complete) data for DOPAMINE (8 total), please visit the HSDB record page.
Dopamine has known human metabolites that include dopamine 3-O-sulfate and Dopamine 4- D-Glucuronide.
Dopamine is a known human metabolite of tyramine.
Biotransformation of dopamine proceeds rapidly to yield the principal excretion products, 3-4-dihydroxy-phenylacetic acid (DOPAC) and 3-methoxy-4-hydroxy-phenylacetic acid (homovanillic acid, HVA).
Route of Elimination: It has been reported that about 80% of the drug is excreted in the urine within 24 hours, primarily as HVA and its sulfate and glucuronide conjugates and as 3,4-dihydroxyphenylacetic acid.
A very small portion is excreted unchanged.
Half Life: 2 minutes

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Biological Half-Life
2 minutes
Plasma dopamine concentrations /of children (age 3 months to 13 yrs) recovering from cardiac surgery or shock/ were measured at the steady state or at termination of infusion using high-performance liquid chromatography. The half-lives of distribution and elimination were 1.8 +/- 1.1 and 26 +/- 14 (SD) mins, respectively.
Dopamine has a plasma half-life of about 2 minutes. In neonates, the elimination half-life of dopamine reportedly is 5-11 minutes.

Toxicity Summary
Dopamine is a precursor to norepinephrine in noradrenergic nerves and is also a neurotransmitter in certain areas of the central nervous system. Dopamine produces positive chronotropic and inotropic effects on the myocardium, resulting in increased heart rate and cardiac contractility. This is accomplished directly by exerting an agonist action on beta-adrenoceptors and indirectly by causing release of norepinephrine from storage sites in sympathetic nerve endings. In the brain, dopamine actas as an agonist to the five dopamine receptor subtypes (D!, D2, D3, D4, D5).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the use of dopamine during breastfeeding. Because of its poor oral bioavailability and short half-life, any dopamine in milk is unlikely to affect the infant. Intravenous dopamine infusion may decrease milk production. Dopamine is known to reduce serum prolactin in nonnursing women, but no information is available on its effect on milk production in nursing mothers.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Intravenous dopamine infusion in doses of 2 to 5 mcg/kg/minute given to nonnursing subjects and in women with hyperprolactinemia decreases serum prolactin concentrations. However, relevant published information on the effect of intravenous dopamine on milk production in nursing mothers was not found as of the revision date. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

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Protein Binding
No information currently available on protein binding.

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Toxicity Data
LD₅₀ oral mice = 1460 mg/kg, LD₅₀ oral rats = 1780 mg/kg

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Interactions
Monoamine oxidase inhibition by furazolidone ... exposes pt to hazards of potential hypertensive crisis if ... other amine-releasing agents /dopamine/ are taken concurrently.
... Possibility of enhanced pharmacological response to phenylephrine and other predominantly direct-acting alpha-adrenergic sympathomimetic amines (eg, dopamine ...) in pt who are receiving or have recently received guanethidine.
Effects on brain dopamine metab in rats studied ; chlorpromazine, thioridazine, and thiethylperazine produced dose-dependent incr in brain concn of 3,4-dihydroxyphenylacetic acid, which were correlated with antipsychotic efficacy.
... Administration of deprenyl inhibits the intracerebral metabolic degradation of dopamine.
For more Interactions (Complete) data for DOPAMINE (12 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat ip 163 mg/kg
LD50 Mouse ip 950 mg/kg
LD50 Mouse iv 59 mg/kg
LD50 Mouse intracervical 74 mg/kg
LD50 Dog iv 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
Cardiotonic Agents
Dopamine also is used to increase cardiac output and blood pressure in advanced cardiovascular life support (ACLS) during cardiopulmonary resuscitation. Dopamine may be considered in the treatment of symptomatic bradycardia unresponsive to atropine, as a temporizing measure while awaiting availability of a pacemaker, or if pacing is ineffective. During resuscitation, dopamine therapy often is used for the management of hypotension, particularly if associated with symptomatic bradycardia or after return of spontaneous circulation. Dopamine combined with other agents, such as dobutamine, also may be a useful option in the management of postresuscitation hypotension. If hypotension persists after filling pressure (i.e., intravascular volume) is optimized, drugs with combined inotropic and vasopressor actions (e.g., epinephrine, norepinephrine) may be used. Some evidence from animal studies suggests that epinephrine may be more effective than dopamine in improving hemodynamics during cardiopulmonary resuscitation. In addition, epinephrine generally is preferred for patients with severe bradycardia and associated hypotension since pulseless electrical activity or even asystole may be imminent. /Included in US product label/
The net hemodynamic effects of dopamine make it particularly useful in the treatment of cardiogenic shock (including that associated with acute myocardial infarction) or in shock in which oliguria is refractory to other vasopressor agents. Some experts state that dopamine may be considered for the treatment of drug-induced hypovolemic shock, and often is the recommended initial agent for this use when the patient is unresponsive to fluid volume expansion and inotropic and/or vasopressor support is required. The drug can be used as an adjunct (to increase cardiac output further and maintain blood pressure) to afterload reduction with vasodilators (e.g., sodium nitroprusside) in patients with left ventricular failure following acute myocardial infarction when arterial pressure decreases precipitously during afterload reduction; for less precipitous decreases, dobutamine may be preferred but should not be used alone in severely hypotensive patients. In patients with hypotensive cardiogenic shock following acute myocardial infarction, dopamine may be used to replace norepinephrine therapy once systemic arterial pressure has increased to at least 80 mm Hg. Once arterial blood pressure has been stabilized to at least 90 mm Hg, dobutamine may be used concomitantly with dopamine in such patients in an attempt to reduce dopamine requirements. Dopamine also has been used to support cardiac output and maintain arterial pressure during intra-aortic balloon counterpulsation therapy (e.g., in patients with hypotensive cardiogenic shock following acute myocardial infarction). The use of dopamine in low cardiac output syndrome following open heart surgery has been shown to increase long-term survival. However, because dobutamine lowers peripheral resistance over a wide dosage range, is not dependent on release of endogenous catecholamines for its effects, and is cardioselective, that drug may be preferable in the period immediately following cardiopulmonary bypass surgery. /Included in US product label/
Dopamine is used to increase cardiac output, blood pressure, and urine flow as an adjunct in the treatment of shock that persists after adequate fluid volume replacement and when systemic vascular resistance is decreased. /Included in US product label/
For more Therapeutic Uses (Complete) data for DOPAMINE (12 total), please visit the HSDB record page.

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Drug Warnings
Dopamine should be used with caution in patients with ischemic heart disease. The drug is contraindicated in patients with pheochromocytoma and in patients with uncorrected tachyarrhythmias or ventricular fibrillation.
Commercially available formulations of dopamine hydrochloride may contain sulfites that can cause allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes, in certain susceptible individuals. The overall prevalence of sulfite sensitivity in the general population is unknown but probably low; such sensitivity appears to occur more frequently in asthmatic than in nonasthmatic individuals.
Caution should be used to avoid extravasation of the drug. Dopamine should be administered through a long IV catheter into a large vein, preferably in the antecubital fossa rather than the hand or ankle. One manufacturer states that administration into an umbilical arterial catheter is not recommended. If larger veins are unavailable and the condition of the patient requires that the hand or ankle veins be used to administer dopamine, the injection site should be changed to a larger vein as soon as possible. The injection site should be carefully monitored.
Patients with a history of occlusive vascular disease (e.g., atherosclerosis, arterial embolism, Raynaud's disease, cold injury, diabetic endarteritis, or Buerger's disease) should be carefully monitored during dopamine therapy for decreased circulation to the extremities indicated by changes in color or temperature of the skin or pain in the extremities. If these occur, they may be corrected by decreasing the rate of infusion or discontinuing dopamine; however, these changes occasionally have persisted and progressed after discontinuing dopamine. The potential benefits of continuing dopamine should be weighed against the possible risk of necrosis.
For more Drug Warnings (Complete) data for DOPAMINE (13 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 to norepinephrine in noradrenergic nerves and is also a neurotransmitter in certain areas of the central nervous system, especially in the nigrostriatal tract, and in a few peripheral sympathetic nerves. Dopamine produces positive chronotropic and inotropic effects on the myocardium, resulting in increased heart rate and cardiac contractility. This is accomplished directly by exerting an agonist action on beta-adrenoceptors and indirectly by causing release of norepinephrine from storage sites in sympathetic nerve endings.

C8H11NO2

153.17844

153.078

51-61-6

Dopamine hydrochloride;62-31-7

681

Light yellow to light brown solid powder

1.2±0.1 g/cm3

337.7±27.0 °C at 760 mmHg

218-220ºC

158.0±23.7 °C

0.0±0.8 mmHg at 25°C

1.619

0.12

3

3

2

11

119

0

VYFYYTLLBUKUHU-UHFFFAOYSA-N

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

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

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

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.)