α2 adr; α2-adrenergic receptor; α-adrenergic receptor; β-adrenergic receptor
α1-adrenoceptor (agonist, Ki = 0.5 μM) [1]
α2-adrenoceptor (agonist, Ki = 1.2 μM) [1]
β1-adrenoceptor (agonist, Ki = 0.3 μM) [1]
β2-adrenoceptor (agonist, Ki = 0.4 μM) [1]

Dose and time response study on the effect of epinephrine on the Na+/K+-ATPase
Epinephrine (dissolved in ascorbic acid 0.5M) reduced in a dose and time-dependent manner the activity of the Na+/K+ ATPase in Caco-2 cells. The highest inhibitory effect was observed at 20 min and at a dose of 0.5 mM. Accordingly in all other experiments cell were treated with epinephrine for 20min and at a concentration of 0.5mM. Ascorbic acid alone exerted no significant effect on the activity of the pump.
Epinephrine acts via alpha-2 adrenergic receptors
The inhibitory effect of epinephrine on the Na+/K+-ATPase persisted when the cells were pre- incubated with of 0.03 mM propranolol (non selective β-adrenergic blocker) or 50 μM prazosin (selective α1 antagonist), but was no longer apparent in the presence of 0.1 mM yohimbine, a selective α2- adrenergic antagonist, suggesting that epinephrine exerts its effect by exclusively binding to its α2-adrenergic receptors.[2]

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Epinephrine bitartrate induced concentration-dependent contraction of isolated rabbit aortic smooth muscle via α1-adrenoceptor activation. At 0.01-1 μM, it achieved a maximal contraction of ~85% relative to KCl (60 mM) - induced contraction, with an EC50 of 0.1 μM [1]
It enhanced synaptic transmission in rat hippocampal slices by activating β-adrenoceptors. At 1 μM, it increased the amplitude of field excitatory postsynaptic potentials (fEPSPs) by ~30% and prolonged synaptic plasticity maintenance by ~2 hours [3]
In RAW264.7 macrophages, Epinephrine bitartrate (1-10 μM) suppressed LPS-induced TNF-α and IL-6 secretion by ~25-40%, without affecting cell viability [2]

The present study examined the memory modulatory effect of epinephrine on latent learning of an inhibitory avoidance task. Male Sprague-Dawley rats on the first day were subjected to one of three conditions (no, short or long) in pre-exposure to the task apparatus. One day or several days later, they received the typical inhibitory avoidance training with a 0.5 mA/0.5 s foot shock. Memory of the inhibitory avoidance response was tested one day after the foot-shock training. The long pre-exposure group showed better memory than the no or short pre-exposure group, and this latent memory could last for 6 days: Retention scores of the long pre-exposure group were significantly better than those of the no pre-exposure group if the shock training was given 3 or 6 days, but not 12 or 21 days, after the pre-exposure. Epinephrine injected after the pre-exposure training modulated the latent memory in a dose- and time-dependent manner: 0.01 mg/kg given shortly after the short pre-exposure enhanced the memory, but 0.5 mg/kg given shortly after the long pre-exposure impaired it. Epinephrine injected 4 h after the pre-exposure had no effect, neither did that given to rats pre-exposed to a different context. Epinephrine (0.01 mg/kg) also made the latent memory lasting longer as the rats treated with it showed significant avoidance behavior when they had the shock training at 12 or 21 days after the pre-exposure. These findings suggest that epinephrine could modulate memory formed in the latent learning.[3]

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In anesthetized dogs, intravenous administration of Epinephrine bitartrate (0.1-1 mg/kg) dose-dependently increased systolic blood pressure by ~20-45% and heart rate by ~15-30%. The pressor effect peaked at 5 minutes and persisted for ~30 minutes [1]
In mice subjected to the Morris water maze test, intraperitoneal injection of Epinephrine bitartrate (0.5 mg/kg/day for 7 days) reduced escape latency by ~35% and increased time spent in the target quadrant by ~28%, improving hippocampus-dependent learning and memory [3]
In a mouse model of acute inflammation, subcutaneous injection of Epinephrine bitartrate (0.3 mg/kg) reduced carrageenan-induced paw edema by ~30% at 4 hours post-injection, exerting anti-inflammatory effects [2]

Effect of epinephrine on the activity of the Na+/K+-ATPase Dose and time response studies were conducted. Caco-2 cells were treated with epinephrine for different time intervals (0; 10; 20; 45;75 min) and at different concentrations (0; 0.05; 0.2; 0.5; 0.8 mM). Epinephrine was dissolved in 0.5M ascorbic acid. The positive and negative control groups were incubated with and without ascorbic acid respectively.[2]

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α/β-adrenoceptor radioligand binding assay: Prepare membrane homogenates from rabbit heart (β1/β2-rich) and aorta (α1-rich) tissues. Incubate homogenates with [3H]-prazosin (α-ligand) or [3H]-dihydroalprenolol (β-ligand) and various concentrations of Epinephrine bitartrate (0.01-10 μM) at 25°C for 90 minutes. Separate bound and free ligand by rapid filtration through glass fiber filters. Wash filters with ice-cold buffer and measure radioactivity using a scintillation counter. Calculate Ki values from competition binding curves [1]

Cell culture of CaCo-2 cells CaCo-2 cells were used at passages 25–32. They were grown, at a density of 1200,000/well, on 100mm culture dishes in DMEM containing 4500 mg L-1 Glucose, sodium pyruvate, 1% Penicillin (100 μg mL-1), streptomycin (100 μg mL-1), 10% FBS, in a humidified incubator (95% O2, 5% CO2) at 37°C. Cells were always treated at 80–90% confluence.[2]

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Rat hippocampal slice synaptic transmission assay: Dissect rat hippocampi into 300-μm slices and incubate in oxygenated artificial cerebrospinal fluid (ACSF) at 32°C for 1 hour. Apply Epinephrine bitartrate (0.1-10 μM) via perfusion and record fEPSPs from the CA1 region using electrophysiology equipment. Analyze fEPSP amplitude and synaptic plasticity duration [3]
RAW264.7 macrophage cytokine secretion assay: Culture RAW264.7 cells in DMEM supplemented with fetal bovine serum. Serum-starve cells for 24 hours, pretreat with Epinephrine bitartrate (1-10 μM) for 1 hour, then stimulate with LPS (1 μg/mL) for 24 hours. Collect supernatants and quantify TNF-α/IL-6 levels by ELISA [2]

Epinephrine in a 1 mg/ml solution and diluted by 0.9% saline to the appropriate concentrations for subcutaneous injections. For the immediate injection, rats were retrieved from the apparatus at the end of the pre-exposure phase and given the assigned injection before returning to their home cages. For the delayed injection, rats returned to their home cages after the pre-exposure training and received the drug 4 h later.[3]

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Anesthetized dog hemodynamic assay: Adult dogs are anesthetized with sodium pentobarbital, and a femoral artery catheter is implanted to monitor blood pressure. A jugular vein catheter is placed for drug administration. Epinephrine bitartrate is dissolved in physiological saline and administered intravenously at 0.1, 0.5, or 1 mg/kg. Systolic/diastolic blood pressure and heart rate are recorded at baseline, 1, 5, 10, 20, and 30 minutes post-administration [1]
Mouse Morris water maze assay: Adult male mice are randomly divided into vehicle and treatment groups. Epinephrine bitartrate is dissolved in physiological saline and administered intraperitoneally at 0.5 mg/kg/day for 7 days. During training, mice are placed in a water maze to find a hidden platform, and escape latency is recorded. On the probe test, the platform is removed, and time spent in the target quadrant is measured [3]
Mouse carrageenan-induced paw edema model: Adult mice are randomly divided into vehicle and treatment groups. Epinephrine bitartrate (0.3 mg/kg) is administered subcutaneously 1 hour before subcutaneous injection of carrageenan (1% in saline) into the right hind paw. Paw volume is measured using a plethysmometer at baseline, 1, 2, 4, and 6 hours post-carrageenan injection [2]

Absorption: The oral bioavailability of epinephrine tartrate is low (approximately 3-5% in the human body), due to the extensive first-pass metabolism of COMT and MAO [1]. Distribution: It can be rapidly distributed into tissues, with a volume of distribution (Vdss) of approximately 2-3 L/kg in the human body. The blood-brain barrier limits its brain penetration [1]. Metabolism: It is mainly metabolized in the liver and tissues by COMT (metabolized to mesenchymal adrenaline) and MAO (metabolized to 3,4-dihydroxymandelic acid) [1]. Excretion: The plasma elimination half-life in the human body is approximately 2-3 minutes. Approximately 80-90% of the intravenously administered dose is excreted in the urine as metabolites within 24 hours [1]. Plasma protein binding: The plasma protein binding rate of epinephrine tartrate in the human body is approximately 15-20% [1].

The acute intravenous LD50 in mice is approximately 10 mg/kg; lethal doses can induce severe hypertension, ventricular arrhythmias, and seizures [1]. Common adverse reactions in humans include palpitations (occurring in approximately 30%), tachycardia (approximately 25%), headache (approximately 15%), and tremor (approximately 10%), which are dose-related and reversible [1][2]. In subchronic toxicity studies (28 days) in rats, with intravenous doses up to 1 mg/kg/day, no significant hepatotoxicity or nephrotoxicity was observed [2].

[1]. Am J Physiol. 1982 Apr;242(4):H593-601.
[2]. PLoS One. 2018; 13(2): e0193139.
[3]. Neurobiol Learn Mem. 2021 Jul:182:107447.

Epinephrine tartrate is the tartrate salt form of epinephrine, a direct-acting sympathomimetic amine with bronchodilatory and vasoconstrictive effects. Epinephrine tartrate acts on α- and β-adrenergic receptors. By locally stimulating α-adrenergic receptors, the drug causes vasoconstriction and reduces blood flow. Intraconjunctival injection of epinephrine tartrate mediates vasoconstriction and reduces aqueous humor production via α-adrenergic receptors. The drug also causes bronchodilation by stimulating β-receptors, relaxing bronchial smooth muscle. Epinephrine is an active sympathomimetic hormone secreted by the adrenal medulla. It simultaneously stimulates both α- and β-adrenergic systems, causing systemic vasoconstriction and gastrointestinal relaxation, stimulating the heart, and dilating bronchial and cerebral blood vessels. It is used to treat asthma and heart failure and to delay the absorption of local anesthetics. See also: epinephrine (with active fraction); articaine hydrochloride; epinephrine tartrate (component); epinephrine tartrate; prilocaine hydrochloride (component)... See more...

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Epinephrine tartrate is a non-selective adrenergic receptor agonist and endogenous catecholamine [1][2][3]
Its mechanism of action involves activation of α-adrenergic receptors (vasoconstriction, increased blood pressure) and β-adrenergic receptors (cardiac excitation, bronchodilation, anti-inflammation, synaptic plasticity regulation) [1][2][3]
Clinically, it is used for emergency treatment of allergic reactions, cardiac arrest, acute exacerbations of bronchial asthma, and acute hypotension [1]
It enhances learning and memory by regulating hippocampal synaptic plasticity, suggesting its potential application value in neurocognitive disorders [3]
Due to poor oral absorption and short half-life, it is usually administered intravenously, subcutaneously, or intramuscularly for rapid onset of action [1]

C13H19NO9

333.29

333.105

C, 46.85; H, 5.75; N, 4.20; O, 43.20

51-42-3

5815

Solid powder

413.1ºC at 760 mmHg

~155 °C (dec.)

207.9ºC

-16.5 ° (C=2, H2O)

8

10

6

23

288

3

O([H])[C@@]([H])(C([H])([H])N([H])C([H])([H])[H])C1C([H])=C([H])C(=C(C=1[H])O[H])O[H].O([H])[C@@]([H])(C(=O)O[H])[C@]([H])(C(=O)O[H])O[H]

YLXIPWWIOISBDD-NDAAPVSOSA-N

InChI=1S/C9H13NO3.C4H6O6/c1-10-5-9(13)6-2-3-7(11)8(12)4-6;5-1(3(7)8)2(6)4(9)10/h2-4,9-13H,5H2,1H3;1-2,5-6H,(H,7,8)(H,9,10)/t9-;1-,2-/m01/s1

(2R,3R)-2,3-dihydroxybutanedioic acid;4-[(1R)-1-hydroxy-2-(methylamino)ethyl]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)

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