Norepinephrine

Overview

Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as a hormone, neurotransmitter and neuromodulator. The name "norepinephrine" (from Ancient Greek ἐπῐ́ (epí), "upon", and νεφρός (nephrós), "kidney") is usually preferred in the United States, whereas "noradrenaline" (from Latin ad, "near", and ren, "kidney") is more commonly used in the United Kingdom and the rest of the world. "Norepinephrine" is also the international nonproprietary name given to the drug. Regardless of which name is used for the substance itself, parts of the body that produce or are affected by it are referred to as noradrenergic.[1][2] WP

The general function of norepinephrine is to mobilize the brain and body for action. Norepinephrine release is lowest during sleep, rises during wakefulness, and reaches much higher levels during situations of stress or danger, in the so-called fight-or-flight response. In the brain, norepinephrine increases arousal and alertness, promotes vigilance, enhances formation and retrieval of memory, and focuses attention; it also increases restlessness and anxiety. In the rest of the body, norepinephrine increases heart rate and blood pressure, triggers the release of glucose from energy stores, increases blood flow to skeletal muscle, reduces blood flow to the gastrointestinal system, and inhibits voiding of the bladder and gastrointestinal motility. WP

In the brain, noradrenaline is produced in nuclei that are small yet exert powerful effects on other brain areas. The most important of these nuclei is the locus coeruleus, located in the pons. Outside the brain, norepinephrine is used as a neurotransmitter by sympathetic ganglia located near the spinal cord or in the abdomen, as well as Merkel cells located in the skin. It is also released directly into the bloodstream by the adrenal glands. Regardless of how and where it is released, norepinephrine acts on target cells by binding to and activating adrenergic receptors located on the cell surface. WP

A variety of medically important drugs work by altering the actions of noradrenaline systems. Noradrenaline itself is widely used as an injectable drug for the treatment of critically low blood pressure. Stimulants often increase, enhance, or otherwise act as agonists of norepinephrine. Drugs such as cocaine and methylphenidate act as reuptake inhibitors of norepinephrine, as do some antidepressants, such as those in the SNRI class. One of the more notable drugs in the stimulant class is amphetamine, which acts as a dopamine and norepinephrine analog, reuptake inhibitor, as well as an agent that increases the amount of global catecholamine signaling throughout the nervous system by reversing transporters in the synapses. Beta blockers, which counter some of the effects of noradrenaline by blocking beta-adrenergic receptors, are sometimes used to treat glaucoma, migraines and a range of cardiovascular diseases. β1Rs preferentially bind epinephrine, along with norepinephrine to a lesser extent and mediates some of their cellular effects in cardiac myocytes such as increased positive inotropy and lusitropy. β-blockers exert their cardioprotective effects through decreasing oxygen demand in cardiac myocytes; this is accomplished via decreasing the force of contraction during systole (negative inotropy) and decreasing the rate of relaxation during diastole (negative lusitropy), thus reducing myocardial energy demand which is useful in treating cardiovascular disorders accompanied by inadequate myocardial oxygen supply. Alpha blockers, which counter the effects of noradrenaline on alpha-adrenergic receptors, are occasionally used to treat hypertension and psychiatric conditions. Alpha-2 agonists often have a sedating and antihypertensive effect and are commonly used as anesthesia enhancers in surgery, as well as in treatment of drug or alcohol dependence. For reasons that are still unclear, some Alpha-2 agonists, such as guanfacine, have also been shown to be effective in the treatment of anxiety disorders and ADHD. Many important psychiatric drugs exert strong effects on noradrenaline systems in the brain, resulting in effects that may be helpful or harmful. WP

Pharmacology

Pharmacology

A large number of important drugs exert their effects by interacting with norepinephrine systems in the brain or body. Their uses include treatment of cardiovascular problems, shock, and a variety of psychiatric conditions. These drugs are divided into: sympathomimetic drugs which mimic or enhance at least some of the effects of norepinephrine released by the sympathetic nervous system; sympatholytic drugs, in contrast, block at least some of the effects. Both of these are large groups with diverse uses, depending on exactly which effects are enhanced or blocked.[3] WP

Norepinephrine itself is classified as a sympathomimetic drug: its effects when given by intravenous injection of increasing heart rate and force and constricting blood vessels make it very useful for treating medical emergencies that involve critically low blood pressure. Surviving Sepsis Campaign recommended norepinephrine as first line agent in treating septic shock which is unresponsive to fluid resuscitation, supplemented by vasopressin and epinephrine. Dopamine usage is restricted only to highly selected patients.[3][4] WP

Beta blockers

These are sympatholytic drugs that block the effects of beta adrenergic receptors while having little or no effect on alpha receptors. They are sometimes used to treat high blood pressure, atrial fibrillation, and congestive heart failure, but recent reviews have concluded that other types of drugs are usually superior for those purposes. Beta blockers may be a viable choice for other cardiovascular conditions, though, including angina and Marfan syndrome. They are also widely used to treat glaucoma, most commonly in the form of eyedrops. Because of their effects in reducing anxiety symptoms and tremor, they have sometimes been used by entertainers, public speakers, and athletes to reduce performance anxiety, although they are not medically approved for that purpose and are banned by the International Olympic Committee.[5–10] WP

However, the usefulness of beta blockers is limited by a range of serious side effects, including slowing of heart rate, a drop in blood pressure, asthma, and reactive hypoglycemia. The negative effects can be particularly severe in people with diabetes.[5][8] WP

Alpha blockers

These are sympatholytic drugs that block the effects of adrenergic alpha receptors while having little or no effect on beta receptors. Drugs belonging to this group can have very different effects, however, depending on whether they primarily block alpha-1 receptors, alpha-2 receptors, or both. Alpha-2 receptors, as described elsewhere in this article, are frequently located on norepinephrine-releasing neurons themselves and have inhibitory effects on them; consequently, blockage of alpha-2 receptors usually results in an increase in norepinephrine release. Alpha-1 receptors are usually located on target cells and have excitatory effects on them; consequently, blockage of alpha-1 receptors usually results in blocking some of the effects of norepinephrine. Drugs such as phentolamine that act on both types of receptors can produce a complex combination of both effects. In most cases when the term "alpha blocker" is used without qualification, it refers to a selective alpha-1 antagonist.[11] WP

Selective alpha-1 blockers have a variety of uses. Since one of their effects is to inhibit the contraction of the smooth muscle in the prostate, they are often used to treat symptoms of benign prostatic hyperplasia. Alpha-blockers also likely help people pass their kidney stones. Their effects on the central nervous system make them useful for treating generalized anxiety disorder, panic disorder, and posttraumatic stress disorder. They may, however, have significant side effects, including a drop in blood pressure.[11–14] WP

Some antidepressants function partly as selective alpha-2 blockers, but the best-known drug in that class is yohimbine, which is extracted from the bark of the African yohimbe tree. Yohimbine acts as a male potency enhancer, but its usefulness for that purpose is limited by serious side-effects including anxiety and insomnia. Overdoses can cause a dangerous increase in blood pressure. Yohimbine is banned in many countries, but in the United States, because it is extracted from a plant rather than chemically synthesized, it is sold over the counter as a nutritional supplement.[15][16] WP

Alpha-2 agonists

These are sympathomimetic drugs that activate alpha-2 receptors or enhance their effects. Because alpha-2 receptors are inhibitory and many are located presynaptically on norepinephrine-releasing cells, the net effect of these drugs is usually to reduce the amount of norepinephrine released. Drugs in this group that are capable of entering the brain often have strong sedating effects, due to their inhibitory effects on the locus coeruleus. Clonidine and guanfacine, for example, are used for the treatment of anxiety disorders and insomnia, and also as a sedative premedication for patients about to undergo surgery. Xylazine, another drug in this group, is also a powerful sedative and is often used in combination with ketamine as a general anaesthetic for veterinary surgery—in the United States it has not been approved for use in humans.[17][18][19] WP

Stimulants and antidepressants

These are drugs whose primary effects are thought to be mediated by different neurotransmitter systems (dopamine for stimulants, serotonin for antidepressants), but many also increase levels of norepinephrine in the brain. Amphetamine, for example, is a stimulant that increases release of norepinephrine as well as dopamine. Monoamine oxidase A inhibitors (MAO-A) are antidepressants that inhibit the metabolic degradation of norepinephrine as well as serotonin and dopamine. In some cases it is difficult to distinguish the norepinephrine-mediated effects from the effects related to other neurotransmitters.[20][21][22] WP⚠ Wikipedia itself has flagged this text: citation needed.

History

History

Early in the twentieth century Walter Cannon, who had popularized the idea of a sympathoadrenal system preparing the body for fight and flight, and his colleague Arturo Rosenblueth developed a theory of two sympathins, sympathin E (excitatory) and sympathin I (inhibitory), responsible for these actions. The Belgian pharmacologist Zénon Bacq as well as Canadian and U.S. pharmacologists between 1934 and 1938 suggested that noradrenaline might be a sympathetic transmitter. In 1939, Hermann Blaschko and Peter Holtz independently identified the biosynthetic mechanism for norepinephrine in the vertebrate body. In 1945 Ulf von Euler published the first of a series of papers that established the role of norepinephrine as a neurotransmitter. He demonstrated the presence of norepinephrine in sympathetically innervated tissues and brain, and adduced evidence that it is the sympathin of Cannon and Rosenblueth.[23–26] WP

Stanley Peart was the first to demonstrate the release of noradrenaline after the stimulation of sympathetic nerves. WP

Toxicity

Chemistry

Formula

C8H11NO3 PC

CAS number

51-41-2 PC

Molar mass (g/mol)

169.18 PC

IUPAC name (computed by PubChem)

4-[(1R)-2-amino-1-hydroxyethyl]benzene-1,2-diol PC

SMILES

C1=CC(=C(C=C1[C@H](CN)O)O)O PC

InChIKey

SFLSHLFXELFNJZ-QMMMGPOBSA-N PC

PubChem CID

439260

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

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