What Are Serotonin and Norepinephrine?

Norepinephrine (INN: Norepinephrine, also known as Noradrenaline, abbreviated NE or NA), formerly known as "nephrine", scientific name 1- (3,4-dihydroxyphenyl) -2-aminoethanol, is the adrenaline removed The substance formed after N-methyl group also belongs to catecholamine in chemical structure. It is both a neurotransmitter, which is mainly synthesized and secreted by post-sympathetic neurons and adrenergic nerve endings in the brain. It is the main transmitter released by the latter, and it is also a hormone synthesized and secreted by the adrenal medulla. Less content. Norepinephrine in circulating blood comes mainly from the adrenal medulla.

Chinese name: Norepinephrine
Foreign name: Noradrenaline (Norepinephrine, NA, NE)

Molecular formula: C8H11NO3
Molecular weight: 169.18
CAS: 51-41-2

Brief introduction of norepinephrine compounds

Noradrenaline Basic Information

Chinese name: norepinephrine

Chinese alias: (R) -4- (2-amino-1-hydroxyethyl) -1,2-benzenediol; n-adrenaline; n-kidney; noradren; nor-renin

English name: (R) -noradrenaline

English alias: ()-Norepinephrine; Norepinephrine; 1,2-Benzenediol, 4- (2-amino-1-hydroxyethyl)-, (R)-; L-Noradrenaline; Levarterenol; Noradrenaline

CAS number: 51-41-2

Molecular formula: C ₈ H ₁₁ NO ₃

Structural formula:

Molecular weight: 169.17800

Exact mass: 169.07400

PSA: 86.71000

LogP: 0.79020

Noradrenaline physicochemical properties

Appearance and properties: Crystal

Density: 1.397 g / cm ³

Melting point: 220-230 ° C

Boiling point: 442.6ºC at 760 mmHg

Flash point: 221.5ºC

Refractive index: 1.66

Stability: Stable, but may be photosensitive. Incompatible with acids, bases and oxidants. Store at -20ºC.

Storage conditions: 2-8ºC

Norepinephrine Safety Information

Packing level: II

Danger category: 6.1

Customs Code: 2922509090

Dangerous Goods Transport Code: UN 2811 6.1 / PG 2

WGK Germany: 3

Danger category code: R26 / 27/28

Safety instructions: S28-S36 / 37-S45

RTECS number: DN5950000

Dangerous goods mark: T +

Noradrenaline production method

It can be made from catechol and chloroacetyl chloride after making it into 3,4-dihydroxy-2-chloroacetophenone and then react with ammonia or urotropine.

Norepinephrine use

Anti-shock vasoactive drugs. It is mainly used to rescue shock caused by acute hypotension and peripheral vasodilation, etc. ^[1] .

Noradrenaline Drug Description

Noradrenaline classification

Circulatory Drugs> Cardiopulmonary resuscitation and anti-shock drugs

Norepinephrine dosage form

Injection: 2mg (1ml), 10mg (2ml) (2mg of norepinephrine tartrate is equivalent to 1mg of norepinephrine).

Noradrenaline pharmacological effects

This product is a strong alpha receptor agonist, which has a weak effect on the 1 receptor and has little effect on the 2 receptor. The agonism of alpha receptors can cause vasoconstriction of arterioles and venules. The degree of vasoconstriction is related to alpha receptors on blood vessels. Skin and mucosal vasoconstriction is the most obvious, followed by renal blood vessels, which have no obvious effect on coronary arteries. This may be related to the increase of cardiac metabolites and the expansion of the coronary arteries against the effect of this product. By the activation of 1 receptor, the myocardial contraction is strengthened, and the heart rate is increased, but the intensity of action is much weaker than that of adrenaline. The range of vasoconstriction caused by receptor agonism is very wide, most notably skin, mucosal blood vessels, and glomeruli, followed by brain, liver, mesentery, and skeletal muscle. Following cardiac excitement, myocardial metabolites adenosine increase, Adenosine can cause coronary arteries to dilate. The alpha-receptor-excited cardiac manifestations are mainly increased myocardial contractility, increased heart rate, and increased cardiac output; overall, due to excessively high pressure, it can cause reflex-excited vagus nerves, slowing heart rate, and reducing heart rate. Application of atropine prevents this heart rate from slowing down. Due to the strong contraction of blood vessels, the peripheral resistance is increased, so the cardiac output is unchanged or decreased. Large doses can also cause arrhythmias, but they are rare. Blood pressure: Peripheral vasoconstriction and increased myocardial contractility increase blood supply, which increases systolic and diastolic blood pressure, and increases pulse pressure slightly. Others: It has a weak effect on other smooth muscles, but it can increase the frequency of uterine contraction of pregnant women and have a weaker effect on the body's metabolism. Only at high doses does blood glucose increase. Because it is difficult to cross the blood-brain barrier, there is little central effect. Excessive or long-term use can shrink capillaries and reduce the amount of hemolysis caused by leakage of body fluids.

Noradrenaline pharmacokinetics

After oral administration, it is completely destroyed in the gastrointestinal tract, poor absorption after subcutaneous injection, and prone to local tissue necrosis; intravenous drip is generally used clinically. The effect is rapid after intravenous administration, and the effect lasts for 1 to 2 minutes after stopping instillation. It is mainly metabolized in the liver, and part of it is converted into inactive metabolites by the action of catechol oxygen methyltransferase (COMT) and monoamine oxidase. Excreted by the kidney, most of which are metabolites, and only a small amount is excreted in the original form.

Noradrenaline dosage

Intravenous drip

Dilute before use, instill 4 10g per minute (WYF if 60kG, 6UG per minute, 0.1g / kg.min) can be interpreted as 0.1 ~ 0.2g / kg.min), adjust the dosage according to the condition. You can add 1 to 2 mg of saline or 5% glucose within 100 ml of intravenous drip. According to the situation, grasp the drip rate. After the blood pressure rises to the required level, slow down the drip rate to maintain the blood pressure in the normal range. If the effect is not good, other booster drugs should be used. For critical cases, it can be diluted with 1 to 2 mg to 10 to 20 ml, and slowly pushed into the vein, while adjusting its dose according to blood pressure. After the blood pressure rises, it is maintained by drip.

oral

To treat upper gastrointestinal bleeding, take 1 to 3 ml (1 to 3 mg) of the injection each time, 3 times a day, and add an appropriate amount of cold saline.

Norepinephrine indications

It is used to treat hypotension caused by acute myocardial infarction, extracorporeal circulation, pheochromocytoma resection, etc .; for shock or hypotension caused by insufficient blood volume, this product is used as an adjuvant treatment to supplement hemolytic volume during emergency treatment to increase blood pressure. Temporary maintenance of cerebral and coronary arterial infusion; until supplemental hemolysis is effective; it can also be used to treat hypotension during spinal canal block and blood pressure maintenance after cardiac arrest and resuscitation.

Norepinephrine adverse reactions

(1) Leakage of medicinal solution can cause local tissue necrosis.

(2) The strong vasoconstriction of this product is enough to reduce the blood flow of living organs, the urine output is reduced after the renal blood flow is sharply reduced, and the lack of tissue blood supply leads to hypoxia and acidosis; when it is used continuously or in large quantities, it can reduce the blood flow to the heart , Peripheral vascular resistance increased, cardiac output decreased, serious consequences.

(3) The reactions that should be paid attention to include whitening of the skin along the venous path during intravenous infusion, local peeling of the injection, skin cyanosis, redness of the skin, and severe dizziness. Although the reactions listed above are rare, the consequences are serious.

(4) Individual patients have rash and facial edema due to allergies.

(5) Arrhythmia may occur in patients with hypoxia, electrolyte imbalance, or organic heart disease or overdose; reflex heart rate slowdown may occur after increased blood pressure.

(6) Pay attention to the following reactions if they persist: anxiety, dizziness, headache, paleness, heavy heartbeat, insomnia, etc.

(7) Severe headaches and high blood pressure, slow heart rate, vomiting or even convulsions may occur when overdose.

(8) Sudden discontinuation of the drug after long-term intravenous infusion of NA may cause a sudden drop in blood pressure, so the drug should be gradually reduced. ^[2]

Can cause inadequate blood supply to important organs, a small number of patients may develop arrhythmia, ischemic necrosis of the extremities. Can cause posterior sternum pain. Sometimes the thyroid can be transiently congested and enlarged. For late pregnancy can induce uterine contractions.

Noradrenaline contraindications

(1) Cross-allergic reactions: those who cannot tolerate other sympathomimetic amines, nor can they tolerate this product.

(2) This product easily passes through the placenta, shrinks uterine blood vessels, reduces blood flow, and causes fetal hypoxia. Pregnant women must weigh the advantages and disadvantages when using this product.

(3) No problems have been found in breastfeeding women using this product.

(4) There is a lack of research on this product in children, but no special problems in application have been found so far.

(5) Long-term or large-scale use of the elderly can reduce cardiac output.

(6) The following situations should be used with caution:

Hypoxia, at this time, this product is easy to cause arrhythmia, such as ventricular tachycardia or ventricular fibrillation;

Occlusive vascular disease, such as arteriosclerosis, diabetes, occlusive vasculitis, etc., can further aggravate vascular occlusion. Generally, intravenous injection below the calf should not be used;

Thrombosis, regardless of internal organs or surrounding tissues, can promote blood supply reduction, aggravation of ischemia, and expansion of infarct size.

Norepinephrine drug interactions

(1) Equivalent to general anesthetics such as chloroform, cyclopropane, and halothane, which can make the myocardium more sensitive to sympathomimetic amines, prone to ventricular arrhythmias, and should not be used together. They must be administered in reduced doses.

(2) With the use of -blockers, their respective effects are reduced. After -blockers, the effect of -blockers is prominent, which can lead to hypertension and bradycardia.

(3) With the use of antihypertensive drugs, the antihypertensive effect is offset or weakened, and the use of methyldopa also enhances the pressure of this product.

(4) With the use of digitalis, it is easy to cause arrhythmia. Pay close attention to ECG monitoring.

(5) Cardiovascular effects are enhanced when used with other sympathomimetic amines.

(6) Used together with ergot preparations such as ergotamine, ergometrine or oxytocin, it can promote the vasoconstriction effect, cause severe hypertension, and the blood volume of peripheral blood vessels decreases sharply.

(7) In combination with tricyclic antidepressants, as it inhibits tissue absorption of this product or enhances the sensitivity of adrenaline receptors, it can strengthen the cardiovascular effect of this product and cause arrhythmia, tachycardia, hypertension or high fever, If it must be combined, start with a small amount of this product and monitor cardiovascular effects.

(8) With the use of thyroid hormone, both effects are enhanced.

(9) Co-administration with torazoline can cause blood pressure drop, followed by excessive rebound rebound of blood pressure, so this product should not be used when overdose is exceeded.

Noradrenaline precautions

1. (1) Hypoxia: easy to cause arrhythmia (such as ventricular tachycardia or ventricular fibrillation). (2) Occlusive vascular disease (such as arteriosclerosis, diabetes, occlusive vasculitis, etc.): can further increase vascular occlusion. (3) Thrombosis: Regardless of internal organs or surrounding tissues, blood supply can be reduced, ischemia can increase, and the scope of infarction can be enlarged. (4) Pregnant women.

2. Cross-allergy: Those who are allergic to other sympathomimetic amines may also be allergic to norepinephrine.

3. The effects of drugs on children: The safety of pediatric medication has not been studied.

4. The effects of drugs on the elderly: Changlang or heavy use can reduce cardiac output.

5. Check and monitor before and after medication and during medication: (1) Arterial pressure: start monitoring every 2 to 3 minutes, and once every 5 minutes after blood pressure stabilizes Tube manometer. (2) If necessary, measure the central venous pressure, pulmonary arterial pressure, and pulmonary capillary wedge pressure. (3) urine output. (4) ECG.

6. When hypotension is accompanied by hypovolemia, noradrenaline should be used only after the blood volume is replenished, but it can be used first or in combination in an emergency to increase blood pressure and prevent insufficient blood supply to the brain and coronary arteries.

7. If used with whole blood or plasma, separate infusions or use a Y-shaped tube to connect two containers for infusion.

8. Norepinephrine should be diluted with 5% glucose injection or 5% glucose sodium chloride chloride injection, but not with sodium chloride injection.

9. Norepinephrine should not be injected subcutaneously or intramuscularly. The site of intravenous infusion is preferably in the forearm vein or femoral vein, and adjusted as needed.

10. Norepinephrine should not be instilled for a long time. If it is really necessary, the infusion site should be changed regularly, and measures should be taken on the pressured part (such as the arm position) to reduce the pressure (such as a cotton pad) before infusion. If the skin along the vein is pale or ischemic necrosis has occurred, in addition to the use of vasodilators, hot compresses should be applied as soon as possible and closed with a large dose of procaine, and the infusion site should be replaced. Children should choose a large vein for administration and the site of administration must be changed regularly.

11. Intravenous administration must prevent the drug solution from leaking out of the blood vessel. Blood pressure must be measured at all times during the administration, and the speed of administration must be adjusted to keep the blood pressure within the normal range. If leakage of the medicinal solution occurs, the leakage should be promptly diluted with 5 to 10 mg of phentolamine with sodium chloride injection to 10 to 15 ml for local infiltration injection, which may be effective within 12 hours. In order to prevent further damage to the tissue, 5 to 10 mg of phentolamine can be added to each 1000 ml of the infusion containing NA, which will not weaken the pressurizing effect of NA.

12. When the drug is stopped, the drip rate should be gradually reduced. Sudden drug withdrawal often causes a sudden drop in blood pressure.

13. Overdose can cause severe headache, elevated blood pressure, slow heart rate, vomiting and even convulsions. At this time, norepinephrine should be stopped, and fluids and electrolytes should be appropriately supplemented. Those with high blood pressure should be given adrenaline blockers such as phentolamine 5, 10 mg intravenously.

14. Noradrenaline is discolored when exposed to light, and should be stored away from light. If the injection is brown or precipitated, it should not be used again.

15. Norepinephrine should not be used in combination with alkaline drugs (such as sulfadiazine sodium, aminophylline, etc.) to avoid failure. In alkaline solutions, if it encounters drugs containing iron ion impurities (such as sodium glutamate, sodium lactate, etc.), it will turn purple, and the pressurizing effect will be reduced.

16. Norepinephrine is no longer used for shock treatment, and its application in shock treatment is only a temporary measure. For example, prolonged or high-dose application will worsen microcirculation disorders and make the disease worse. Now advocate more with norepinephrine. Receptor blocker phentolamine is used in combination to antagonize vasoconstriction and retain the effect of norepinephrine-stimulated beta receptors ^[3] .

Norepinephrine Expert Review

Norepinephrine is mainly used for shocks caused by various causes, including cardiogenic shock, low-exhaustion and low-resistance (warm) shock. Clinically, the lowest effective amount and the shortest possible time are used. Because large doses of norepinephrine adrenaline are applied for too long, it can cause strong contraction of peripheral and splanchnic blood vessels, reduce blood flow in the splanchnic vascular bed, and cause adverse consequences such as oliguria, urinary closure, tubular necrosis, and liver necrosis ^{[ 3]} .

Norepinephrine Additional Information

The difference between norepinephrine and norepinephrine

Adrenaline and norepinephrine in the blood are mainly secreted by the adrenal medulla. The effects of the two on the heart and blood vessels are both common and special because they are different from the adrenal glands on the membranes of the heart muscle and vascular smooth muscle. Serotonin receptors, due to different binding capabilities.

After adrenaline binds to the corresponding receptors on the membrane of myocardial cells, it increases the heart rate, increases the contractility of the myocardium, and increases the cardiac output. It is often used clinically as a first-aid medicine for the heart; after binding to the corresponding receptors on the membrane of vascular smooth muscle cells, it makes the skin and kidney Gastrointestinal vasoconstriction, but for skeletal muscle and liver vessels, physiological concentration makes them relax, and it contracts at high doses, so normal physiological concentration of epinephrine has little effect on peripheral resistance. Norepinephrine can also significantly increase myocardial contractility, increase heart rate, and increase cardiac output; cause small arteries other than coronary arteries to contract strongly, causing peripheral resistance to increase significantly and blood pressure to increase. Pressure application. At higher doses, the peripheral resistance is significantly increased due to the strong contraction of the blood vessels, so the systolic blood pressure is increased while the diastolic blood pressure is also increased, and the pulse pressure becomes smaller. However, a slow heart rate usually occurs after intravenous administration of norepinephrine to a whole body. This is due to the effect that norepinephrine can significantly increase peripheral resistance and increase hypertension, which slows heart rate through baroreceptor reflexes, thereby masking the direct effect of norepinephrine on the heart.

Function: It mainly activates receptors, and has very weak agonistic effects on 1 receptors. It has almost no effect on 2 receptors. It has a strong vasoconstriction effect, causing both small arteries and veins in the whole body to contract (but coronary vessels dilate) Increased peripheral resistance and increased blood pressure. Exciting the heart and inhibiting smooth muscle are weaker than epinephrine. Clinically, it mainly uses its pressure-increasing effect, and intravenous drip is used in various shocks to increase blood pressure and ensure blood supply to important organs (such as the brain). The use time should not be too long, otherwise it can cause the blood vessels to continue to contract strongly and make the tissue hypoxia worse. The use of phentolamine to combat excessively strong vasoconstrictive effects can often improve tissue blood supply during shock. Epinephrine is an agonist of and receptors, which will increase blood pressure due to the vasoconstrictor effect. Phentolamine is an alpha receptor blocker that can selectively block alpha receptors related to vasoconstriction, while beta receptors related to vasodilation are not blocked. Tolamin will have a drop in blood pressure, called the inverse effect of adrenaline ^[4] .

Norepinephrine memory repair

Earlier studies have shown that the lack of goal-oriented behavior in patients with schizophrenia may be related to a functional deficit in their cortical norepinephrine system. The role of norepinephrine in learning and memory has also been vague and controversial. A long-standing hypothesis suggests that the adrenergic nervous system mediates the memory-strengthening component of emotional events. The researchers tested this hypothesis in several learning tasks using mice with conditionally deficient norepinephrine and epinephrine mutants and rats and mice treated with adrenergic receptors with antagonist drugs and potentiators. . The discovery of adrenaline signaling is essential for the repair of intermediary relationships and spatial memory, but it is not necessary for the repair or consolidation of general emotional memory. Noradrenaline's role in repair requires signaling through the beta-adrenergic receptor in the hippocampus. These results demonstrate that the mechanisms of memory repair can diversify the end-of-memory time and can be different from those of memory acquisition or consolidation. These findings may be related to the symptoms of several psychiatric disorders and heart failure with blockers.