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DEA NFLIS-Drug Category -> Phenethylamines

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals

Pharmaceuticals -> Sympathomimetics

log Kow = -0.98

-0.98

-0.97

Freely sol in water; sol in methanol, in hot 95% ethanol, in aq soln of alkali hydroxides; practically insol in petroleum ether, ether, benzene, chloroform, toluene /Hydrochloride/

Freely soluble in water, methanol, and hot 95% ethanol but is practically insoluble in ether, petroleum ether, chloroform, benzene, and toluene.

535 mg/mL

Breast Feeding; Lactation; Milk, Human; Cardiotonic Agents; Catecholamines; Dopamine Agents; Sympathomimetics

Pharmaceuticals

Medicines used in heart failure

Highly sensitive to oxygen; discolors quickly

Extremely unstable in alkaline media; sensitive to light; stable for 1 yr at 55 °C /Hydrochloride/

Positive

2.72

2.7

Agilent XCT

Electrospray ionization

formic acid (5.3nM)

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P264, P270, P273, P280, P301+P317, P318, P330, P391, P405, and P501 (click each P-code to see the statement)

The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl dopamine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Dopamine hydrochloride/

Water spray, dry chemical, carbon dioxide or foam as appropriate for surrounding fire and materials. This material is assumed to be combustible. As with all dry powders it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity. As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing. /Dopamine hydrochloride/

Some commercially available injections of dopamine in dextrose provided in plastic containers should be stored at room temperature (25 °C), although brief exposure to temperatures up to 40 °C does not adversely affect the injections; the injections should be protected from excessive heat and should not be frozen..

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

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.

Signs and Symptoms of Overdose or Toxicity

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).

/SIGNS AND SYMPTOMS/ Possible allergic reaction to material if inhaled, ingested, or in contact with skin. /Dopamine hydrochloride/

/SIGNS AND SYMPTOMS/ Overdose effects include severe increase in blood pressure. /Dopamine hydrochloride/

/SIGNS AND SYMPTOMS/ Extravasation of large amt of dopamine into local tissue may cause ischemic necrosis and slough. Gangrene of fingers and toes after prolonged infusion has been reported.

/SIGNS AND SYMPTOMS/ Ventricular arrhythmias and hypertension may occur when usual doses of dopamine are administered during halothane (or other halogenated hydrocarbon) or cyclopropane anesthesia. Extreme caution should be used when administering dopamine to patients receiving these general anesthetics which increase cardiac irritability. Results of studies in animals indicate that dopamine-induced ventricular arrhythmias during anesthesia can be reversed by propranolol.

For more Human Toxicity Excerpts (Complete) data for DOPAMINE (12 total), please visit the HSDB record page.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

dopamine

DILI Negative

Intravenous

DOI:10.1016/j.drudis.2019.09.022

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Reproduction studies in rats and rabbits using IV dopamine hydrochloride dosages up to 6 mg/kg daily during organogenesis have not revealed evidence of teratogenicity or embryotoxicity; however, maternal toxicity (e.g., decreased body weight gain, death) was observed in rats. In a study in rats, subcutaneous dosages of 10 mg/kg for 30 days markedly prolonged metestrus and increased mean pituitary and ovary weights. After similar administration to pregnant rats, either throughout gestation or for 5 days beginning on day 10 or 15 of gestation, decreased body weight gain, increased mortality, and slight increases in cataract formation occurred in the offspring.

/GENOTOXICITY/ In the in vivo mouse and male rat bone marrow micronucleus tests, no clear evidence of clastogenic potential was found at IV dosages up to 224 and 30 mg/kg of dopamine hydrochloride, respectively.

/GENOTOXICITY/ In a mammalian mutagenicity assay using L5178Y TK+ mouse lymphoma cells, dopamine was associated with toxicity and increases in mutant frequencies at concentrations of 750 mcg/mL without metabolic activation and 3000 mcg/mL with activation. No increases in mutant frequencies occurred at lower concentrations.

/GENOTOXICITY/ In the Ames microbial (Salmonella) mutagen test (with or without metabolic activation), there was a reproducible dose-dependent increase in the number of revertant colonies with strains TA100 and TA98 at dopamine dosages approaching maximal solubility. However, such small increases were considered inconclusive evidence of mutagenicity.

For more Non-Human Toxicity Excerpts (Complete) data for DOPAMINE (9 total), please visit the HSDB record page.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl dopamine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Dopamine hydrochloride/

C - Cardiovascular system

QC - Cardiovascular system

C01CA04

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.

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 acts as an agonist to the five dopamine receptor subtypes (D1, D2, D3, D4, D5).

Dopamine acts on cardiac beta-1-adrenergic receptors and has dosage-dependent effects on peripheral receptors. Dopamine receptors are activated at a low infusion rate (0.5-2 ug/kg/min). At a rate > 4-6 ug/kg/min, peripheral alpha-adrenergic receptors are activated, and vasoconstriction and increased afterload may occur.

The effects that dopamine produces in the body are directly related to its actions on alpha, beta, and dopaminergic receptor sites. When these receptors are stimulated cyclic adenosine monophosphate levels increase, increasing calcium transport into the cell. The amount of dopamine determines which receptors are predominantly stimulated. At infusion rates more than 5 to 10 ug/kg/minute, alpha-receptor stimulation predominates, resulting in peripheral vasoconstriction, with a rise in blood pressure. At infusion rates greater than 20 ug/kg/minute, the vasoconstrictive effect can be greater than the beta1 effect.

The cardiovascular effects of dopamine are mediated by several distinct types of receptors that vary in their affinity for dopamine. At low concentrations, the primary interaction of dopamine is with vascular D1 receptors, especially in the renal, mesenteric, and coronary beds. By activating adenylyl cyclase and raising intracellular concentrations of cyclic AMP, D1 receptor stimulation leads to vasodilation. Infusion of low doses of dopamine causes an increase in glomerular filtration rate, renal blood flow, and Na+ excretion. Activation of D1 receptors on renal tubular cells decreases sodium transport by cAMP-dependent and cAMP-independent mechanisms. Increasing cAMP production in the proximal tubular cells and the medullary part of the thick ascending limb of the loop of Henle inhibits the Na+-H+ exchanger and the Na+,K+-ATPase pump. The renal tubular actions of dopamine that cause natriuresis may be augmented by the increase in renal blood flow and the small increase in the glomerular filtration rate that follow its administration. The resulting increase in hydrostatic pressure in the peritubular capillaries and reduction in oncotic pressure may contribute to diminished reabsorption of sodium by the proximal tubular cells.

At somewhat higher concentrations, dopamine exerts a positive inotropic effect on the myocardium, acting on beta1 adrenergic receptors. Dopamine also causes the release of norepinephrine from nerve terminals, which contributes to its effects on the heart. Tachycardia is less prominent during infusion of dopamine than of isoproterenol. Dopamine usually increases systolic blood pressure and pulse pressure and either has no effect on diastolic blood pressure or increases it slightly. Total peripheral resistance usually is unchanged when low or intermediate doses of dopamine are given, probably because of the ability of dopamine to reduce regional arterial resistance in some vascular beds, such as mesenteric and renal, while causing only minor increases in others. At high concentrations, dopamine activates vascular alpha1 receptors, leading to more general vasoconstriction.

For more Mechanism of Action (Complete) data for DOPAMINE (9 total), please visit the HSDB record page.

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.

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.

VTD58H1Z2X

DOPAMINE

Established Pharmacologic Class [EPC] - Catecholamine

Chemical Structure [CS] - Catecholamines

Dopamine is a Catecholamine.

DOPAMINE

Agents that have a strengthening effect on the heart or that can increase cardiac output. They may be CARDIAC GLYCOSIDES; SYMPATHOMIMETICS; or other drugs. They are used after MYOCARDIAL INFARCT; CARDIAC SURGICAL PROCEDURES; in SHOCK; or in congestive heart failure (HEART FAILURE).

Drugs that mimic the effects of stimulating postganglionic adrenergic sympathetic nerves. Included here are drugs that directly stimulate adrenergic receptors and drugs that act indirectly by provoking the release of adrenergic transmitters.

Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons.

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.

... used in the treatment of severe congestive /heart/ failure ... also may improve physiological parameters in the treatment of cardiogenic and septic shock

For the correction of hemodynamic imbalances present in shock ... due to mycocardial infarction, trauma, endotoxin septicemia, open-heart surgery, and chronic cardiac decompensation as in congestive failure

Therapeutic Category: Cardiotonic; antihypotensive

Medication

Use (kg; approx.) in Germany (2009): >25

For the correction of hemodynamic imbalances present in the shock syndrome due to myocardial infarction, trauma, endotoxic septicemia, open-heart surgery, renal failure, and chronic cardiac decompensation as in congestive failure

Dopamine is synthesized from veratrole by chloromethylation to form veratryl chloride, followed by cyanation, catalytic hydrogenation, and demethylation.

Prepared from aminotyramine ... ; from homoveratrylamine.

Table: Dopamine Hydrochloride Preparations [Table#4379]

Table: Dopamine Hydrochloride in Dextrose Preparations [Table#4380]

One of the catecholamine neurotransmitters in the brain. ... important in regulating movement

The compatability of dopamine hydrochloride with various additives in 5% dextrose injection USP was established.