Norepinephrine
Encyclopedia
Norepinephrine (abbreviated norepi or NE) is the US name for noradrenaline (BAN
British Approved Name
A British Approved Name is the official non-proprietary or generic name given to a pharmaceutical substance, as defined in the British Pharmacopoeia...

) (abbreviated NA or NAd), a catecholamine
Catecholamine
Catecholamines are molecules that have a catechol nucleus consisting of benzene with two hydroxyl side groups and a side-chain amine. They include dopamine, as well as the "fight-or-flight" hormones adrenaline and noradrenaline released by the adrenal medulla of the adrenal glands in response to...

 with multiple roles including as a hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

 and a neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

. Areas of the body that produce or are affected by norepinephrine are described as noradrenergic.

The terms noradrenaline (from the Latin) and norepinephrine (derived from Greek) are interchangeable, with noradrenaline the common name in most parts of the world. However, to avoid confusion and achieve consistency medical authorities have promoted norepinephrine as the favoured nomenclature, and this is the term used throughout this article.

One of the most important functions of norepinephrine is its role as the neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

 released from the sympathetic neurons affecting the heart. An increase in norepinephrine from the sympathetic nervous system increases the rate of contractions.

As a stress hormone
Stress hormone
Stress hormones such as cortisol, GH and norepinephrine are released at periods of high stress. The hormone regulating system is known as the endocrine system...

, norepinephrine affects parts of the brain, such as the amygdala
Amygdala
The ' are almond-shaped groups of nuclei located deep within the medial temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing and memory of emotional reactions, the amygdalae are considered part of the limbic system.-...

, where attention
Attention
Attention is the cognitive process of paying attention to one aspect of the environment while ignoring others. Attention is one of the most intensely studied topics within psychology and cognitive neuroscience....

 and responses are controlled. Along with epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...

, norepinephrine also underlies the fight-or-flight response
Fight-or-flight response
The fight-or-flight response was first described by Walter Bradford Cannon....

, directly increasing heart rate
Heart rate
Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....

, triggering the release of glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

 from energy stores, and increasing blood flow to skeletal muscle
Skeletal muscle
Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...

. It increases the brain's oxygen supply. Norepinephrine can also suppress neuroinflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

 when released diffusely in the brain from the locus coeruleus.

When norepinephrine acts as a drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...

, it increases blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...

 by increasing vascular tone (tension of muscles) through α-adrenergic receptor
Adrenergic receptor
The adrenergic receptors are a class of metabotropic G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline and adrenaline ....

 activation. The resulting increase in vascular resistance
Vascular resistance
Vascular resistance is a term used to define the resistance to flow that must be overcome to push blood through the circulatory system. The resistance offered by the peripheral circulation is known as the systemic vascular resistance , while the resistance offered by the vasculature of the lungs...

 triggers a compensatory reflex
Reflex
A reflex action, also known as a reflex, is an involuntary and nearly instantaneous movement in response to a stimulus. A true reflex is a behavior which is mediated via the reflex arc; this does not apply to casual uses of the term 'reflex'.-See also:...

 that overcomes the direct homeostatic effect of that increase on the heart, called the baroreceptor reflex, which otherwise would result in a drop in heart rate called reflex bradycardia
Reflex bradycardia
Reflex bradycardia is a bradycardia in response to the baroreceptor reflex, one of the body's homeostatic mechanisms for preventing abnormal increases blood pressure...

.

Norepinephrine is synthesized from dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 by dopamine β-hydroxylase. It is released from the adrenal medulla
Adrenal medulla
The adrenal medulla is part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex. It is the innermost part of the adrenal gland, consisting of cells that secrete epinephrine , norepinephrine , and a small amount of dopamine in response to...

 into the blood as a hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

, and is also a neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

 in the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 and sympathetic nervous system
Sympathetic nervous system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...

, where it is released from noradrenergic neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

s in the locus coeruleus. The actions of norepinephrine are carried out via the binding to adrenergic receptor
Adrenergic receptor
The adrenergic receptors are a class of metabotropic G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline and adrenaline ....

s.

Chemistry

Norepinephrine is a catecholamine
Catecholamine
Catecholamines are molecules that have a catechol nucleus consisting of benzene with two hydroxyl side groups and a side-chain amine. They include dopamine, as well as the "fight-or-flight" hormones adrenaline and noradrenaline released by the adrenal medulla of the adrenal glands in response to...

 and a phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...

. The natural stereoisomer is L-(−)-(R)-norepinephrine. The term "norepinephrine" is derived from the chemical prefix nor-
Nor-
In chemical nomenclature, nor is a prefix to name a structural analog that can be derived from a parent compound by the removal of one carbon atom along with the accompanying hydrogen. The nor-compound can be derived by demethylation or by removal of a methylenegroup, a CH group or a C atom...

, which indicates that norepinephrine is the next-lower homolog
Homology (chemistry)
In chemistry, homology refers to the appearance of homologues. A homologue is a compound belonging to a series of compounds differing from each other by a repeating unit, such as a methylene group, a peptide residue, etcetera....

 of epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...

. The two structures differ only in that epinephrine has a methyl group attached to its nitrogen, whereas the methyl group is replaced by a hydrogen atom in norepinephrine. The prefix nor-
Nor-
In chemical nomenclature, nor is a prefix to name a structural analog that can be derived from a parent compound by the removal of one carbon atom along with the accompanying hydrogen. The nor-compound can be derived by demethylation or by removal of a methylenegroup, a CH group or a C atom...

is likely derived as an abbreviation of the word "normal", used to indicate a demethylated compound.

Origins

Norepinephrine is released when a host of physiological
Physiology
Physiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...

 changes are activated by a stressful event.

In the brain, this is caused in part by activation of an area of the brain stems called the locus ceruleus
Locus ceruleus
The locus coeruleus , is a nucleus in the brainstem involved with physiological responses to stress and panic. It was discovered in the 18th century by Félix Vicq-d'Azyr....

. This nucleus is the origin of most norepinephrine pathways in the brain. Noradrenergic neurons project bilaterally (send signals to both sides of the brain) from the locus ceruleus along distinct pathways to many locations, including the cerebral cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...

, limbic system
Limbic system
The limbic system is a set of brain structures including the hippocampus, amygdala, anterior thalamic nuclei, septum, limbic cortex and fornix, which seemingly support a variety of functions including emotion, behavior, long term memory, and olfaction. The term "limbic" comes from the Latin...

, and the spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...

, forming a neurotransmitter system.

Norepinephrine is also released from postganglionic neurons of the sympathetic nervous system
Sympathetic nervous system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...

, to transmit the fight-or-flight response in each tissue, respectively. The adrenal medulla
Adrenal medulla
The adrenal medulla is part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex. It is the innermost part of the adrenal gland, consisting of cells that secrete epinephrine , norepinephrine , and a small amount of dopamine in response to...

 can also be counted to such postganglionic nerve cells, although they release norepinephrine into the blood.

Norepinephrine system

The noradrenergic neurons in the brain form a neurotransmitter system, that, when activated, exerts effects on large areas of the brain. The effects are alertness and arousal
Arousal
Arousal is a physiological and psychological state of being awake or reactive to stimuli. It involves the activation of the reticular activating system in the brain stem, the autonomic nervous system and the endocrine system, leading to increased heart rate and blood pressure and a condition of...

, and influences on the reward system
Reward system
In neuroscience, the reward system is a collection of brain structures which attempts to regulate and control behavior by inducing pleasurable effects...

.

The noradrenergic neurons originate both in the locus coeruleus and the lateral tegmental field. The axons of the neurons in the locus coeruleus act on adrenergic receptors in:
  • Amygdala
    Amygdala
    The ' are almond-shaped groups of nuclei located deep within the medial temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing and memory of emotional reactions, the amygdalae are considered part of the limbic system.-...

  • Cingulate gyrus
  • Cingulum
    Cingulum
    The cingulum is a collection of white matter fibers projecting from the cingulate gyrus to the entorhinal cortex in the brain, allowing for communication between components of the limbic system....

  • Hippocampus
    Hippocampus
    The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...

  • Hypothalamus
    Hypothalamus
    The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

  • Neocortex
    Neocortex
    The neocortex , also called the neopallium and isocortex , is a part of the brain of mammals. It is the outer layer of the cerebral hemispheres, and made up of six layers, labelled I to VI...

  • Spinal cord
    Spinal cord
    The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...

  • Striatum
    Striatum
    The striatum, also known as the neostriatum or striate nucleus, is a subcortical part of the forebrain. It is the major input station of the basal ganglia system. The striatum, in turn, gets input from the cerebral cortex...

  • Thalamus
    Thalamus
    The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...



On the other hand, axons of neurons of the lateral tegmental field act on adrenergic receptor
Adrenergic receptor
The adrenergic receptors are a class of metabotropic G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline and adrenaline ....

s in hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

, for example.

This structure explains some of the clinical uses of norepinephrine, since a modification of the system affects large areas of the brain.

Mechanism

Norepinephrine is synthesized from tyrosine
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...

 as a precursor, and packed into synaptic vesicles. It performs its action by being released into the synaptic cleft, where it acts on adrenergic receptors, followed by the signal termination, either by degradation of norepinephrine or by uptake by surrounding cells.

Biosynthesis

Norepinephrine is synthesized by a series of enzymatic steps in the adrenal medulla
Adrenal medulla
The adrenal medulla is part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex. It is the innermost part of the adrenal gland, consisting of cells that secrete epinephrine , norepinephrine , and a small amount of dopamine in response to...

 and postganglionic neurons of the sympathetic nervous system
Sympathetic nervous system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...

 from the amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 tyrosine
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...

:

Vesicular transport

Between the decarboxylation and the final β-oxidation, norepinephrine is transported into synaptic vesicle
Synaptic vesicle
In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...

s. This is accomplished by vesicular monoamine transporter
Vesicular monoamine transporter
The vesicular monoamine transporter is a transport protein integrated into the membrane of intracellular vesicles of presynaptic neurons. It acts to transport monoamines into the synaptic vesicles.-Monoamines:...

 (VMAT) in the lipid bilayer
Lipid bilayer
The lipid bilayer is a thin membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around cells. The cell membrane of almost all living organisms and many viruses are made of a lipid bilayer, as are the membranes surrounding the cell nucleus...

. This transporter has equal affinity for norepinephrine, epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...

 and isoprenaline.

Release

To perform its functions, norepinephrine must be released from synaptic vesicles. Many substances modulate this release, some inhibiting it and some stimulating it.

For instance, there are inhibitory α2 adrenergic receptors presynaptically that give negative feedback
Negative feedback
Negative feedback occurs when the output of a system acts to oppose changes to the input of the system, with the result that the changes are attenuated. If the overall feedback of the system is negative, then the system will tend to be stable.- Overview :...

 on release by homotropic modulation.

Receptor binding

Norepinephrine performs its actions on the target cell by binding to and activating adrenergic receptor
Adrenergic receptor
The adrenergic receptors are a class of metabotropic G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline and adrenaline ....

s. The target cell expression of different types of receptors determines the ultimate cellular effect, and thus norepinephrine has different actions on different cell type
Cell type
A cell type is a distinct morphological or functional form of cell. When a cell switches state from one cell type to another, it undergoes cellular differentiation. A list of distinct cell types in the adult human body may include several hundred distinct types.-References:...

s.

Uptake

Extracellular uptake of norepinephrine into the cytosol is done either presynaptically (uptake 1) or by non-neuronal cells in the vicinity (uptake 2). Furthermore, there is a vesicular uptake mechanism from the cytosol into synaptic vesicles.
Comparison of norepinephrine uptake
Uptake Transporter Vmax (n
Nano
Nano- is a prefix meaning a billionth. Used primarily in the metric system, this prefix denotes a factor of 10−9 or . It is frequently encountered in science and electronics for prefixing units of time and length, such as 30 nanoseconds , 100 nanometres or in the case of electrical capacitance,...

mol
Mol
-Places:* City Municipality of Ljubljana, known after the acronym MOL in Slovene language * Märkisch-Oderland, a rural district of Brandenburg, Germany* Mol, Belgium, a municipality in Belgium* Mol, Serbia, a town in Serbia...

/g/min)
KM Specificity Location Other substrates Inhibitors
Uptake 1 Norepinephrine transporter
Norepinephrine transporter
The norepinephrine transporter , also known as solute carrier family 6 member 2 , is a protein that in humans is encoded by the SLC6A2 gene....

 
1.2 0.3 norepinephrine > epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...

 > isoprenaline 
presynaptic
  • methylnoradrenaline (nasal decongestant
    Decongestant
    A decongestant or nasal decongestant is a type of drug that is used to relieve nasal congestion.-Pharmacology:The vast majority of decongestants act via enhancing norepinephrine and epinephrine or adrenergic activity by stimulating the α-adrenergic receptors...

    )
  • tyramine
    Tyramine
    Tyramine is a naturally occurring monoamine compound and trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent...

  • guanethidine
    Guanethidine
    Guanethidine is an antihypertensive drug that reduces the release of catecholamines, such as norepinephrine. Guanethidine is transported across the sympathetic nerve membrane by the same mechanism that transports norepinephrine itself , and uptake is essential for the drug's action...

  • Cocaine
    Cocaine
    Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...

  • Tricyclic antidepressant
    Tricyclic antidepressant
    Tricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms...

    s (e.g. desipramine
    Desipramine
    Desipramine is a tricyclic antidepressant . It inhibits the reuptake of norepinephrine and to a lesser extent serotonin. It is used to treat depression, but not considered a first line treatment since the introduction of SSRI antidepressants...

    )
  • Phenoxybenzamine
    Phenoxybenzamine
    Phenoxybenzamine is a non-selective, irreversible alpha antagonist.-Uses:It is used in the treatment of hypertension, and specifically that caused by pheochromocytoma...

  • Amphetamine
    Amphetamine
    Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...

  • Uptake 2 100 250 epinephrine
    Epinephrine
    Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...

     > norepinephrine > isoprenaline 
    cell membrane
    Cell membrane
    The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

     of non-neuronal cells
  • dopamine
    Dopamine
    Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

  • 5-HT
  • histamine
    Histamine
    Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...

  • normetanephrine
    Normetanephrine
    Normetanephrine is a metabolite of norepinephrine created by action of catechol-O-methyl transferase on norepinephrine. It is excreted in the urine and found in certain tissues. It is a marker for catecholamine-secreting tumors such as pheochromocytoma....

  • steroid hormone
    Steroid hormone
    A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens...

    s (e.g., corticosterone
    Corticosterone
    Corticosterone is a 21-carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands.-Roles:In many species, including amphibians, reptiles, rodents and birds, corticosterone is a main glucocorticoid, involved in regulation of fuel, immune reactions, and stress...

    )
  • phenoxybenzamine
    Phenoxybenzamine
    Phenoxybenzamine is a non-selective, irreversible alpha antagonist.-Uses:It is used in the treatment of hypertension, and specifically that caused by pheochromocytoma...

  • Vesicular VMAT
    Vesicular monoamine transporter
    The vesicular monoamine transporter is a transport protein integrated into the membrane of intracellular vesicles of presynaptic neurons. It acts to transport monoamines into the synaptic vesicles.-Monoamines:...

    - ~0.2 norepinephrine > epinephrine > isoprenaline Synaptic vesicle
    Synaptic vesicle
    In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...

     membrane
  • dopamine
  • 5-HT
  • guanethidine
  • MPP+
    MPP+
    MPP+ is a positively charged molecule with chemical formula C12H12N+. It is toxic and acts by interfering with oxidative phosphorylation in mitochondria, causing depletion of ATP and cell death...

  • Reserpine
    Reserpine
    Reserpine is an indole alkaloid antipsychotic and antihypertensive drug that has been used for the control of high blood pressure and for the relief of psychotic symptoms, although because of the development of better drugs for these purposes and because of its numerous side-effects, it is rarely...

  • Tetrabenazine
    Tetrabenazine
    Tetrabenazine is a drug for the symptomatic treatment of hyperkinetic movement disorder and is marketed under the trade names Nitoman in Canada and Xenazine in New Zealand and some parts of Europe, and is also available in the USA as an orphan drug. On August 15, 2008 the U.S...


  • Degradation

    In mammals, norepinephrine is rapidly degraded to various metabolite
    Metabolite
    Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...

    s. The principal metabolites are:
    • Normetanephrine
      Normetanephrine
      Normetanephrine is a metabolite of norepinephrine created by action of catechol-O-methyl transferase on norepinephrine. It is excreted in the urine and found in certain tissues. It is a marker for catecholamine-secreting tumors such as pheochromocytoma....

       (via the enzyme catechol-O-methyl transferase, COMT
      Catechol-O-methyl transferase
      Catechol-O-methyltransferase is one of several enzymes that degrade catecholamines such as dopamine, epinephrine, and norepinephrine. In humans, catechol-O-methyltransferase protein is encoded by the COMT gene...

      )
    • 3,4-Dihydroxymandelic acid
      3,4-Dihydroxymandelic acid
      3,4-Dihydroxymandelic acid is a metabolite of norepinephrine.-References:...

       (via monoamine oxidase, MAO)
    • Vanillylmandelic acid (3-Methoxy-4-hydroxymandelic acid), also referred to as vanilmandelate or VMA (via MAO)
    • 3-Methoxy-4-hydroxyphenylethylene glycol, "MHPG" or "MOPEG" (via MAO)
    • Epinephrine
      Epinephrine
      Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...

       (via PNMT
      Phenylethanolamine N-methyltransferase
      Phenylethanolamine N-methyltransferase is an enzyme found in the adrenal medulla that converts Norepinephrine to Epinephrine .PNMT is positively influenced by cortisol, which is produced in the adrenal cortex....

      )


    In the periphery, VMA is the major metabolite of catecholamines, and is excreted unconjugated in the urine. A minor metabolite (although the major one in the central nervous system) is MHPG, which is partly conjugated to sulfate or glucuronide derivatives and excreted in the urine.

    By indication

    Norepinephrine may be used for the indications attention-deficit/hyperactivity disorder, depression, and hypotension. Norepinephrine, as with other catecholamines, itself cannot cross the blood-brain barrier, so drugs such as amphetamines are necessary to increase brain levels.

    Attention-deficit/hyperactivity disorder

    Norepinephrine, like dopamine
    Dopamine
    Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

    , has come to be recognized as playing a large role in attention and focus. For people with ADHD, psychostimulant medications such as methylphenidate
    Methylphenidate
    Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...

     (Ritalin/Concerta), dextroamphetamine
    Dextroamphetamine
    Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....

     (Dexedrine), and Adderall
    Adderall
    Adderall is a brand name of amphetamine salts–based medication used for attention-deficit hyperactivity disorder and narcolepsy. It is a brand-name psychostimulant medication composed of racemic amphetamine aspartate monohydrate, racemic amphetamine sulfate, dextroamphetamine saccharide, and...

     (a mixture of dextroamphetamine and racemic
    Racemic
    In chemistry, a racemic mixture, or racemate , is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule. The first known racemic mixture was "racemic acid", which Louis Pasteur found to be a mixture of the two enantiomeric isomers of tartaric acid.- Nomenclature :A...

     amphetamine
    Amphetamine
    Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...

     salts) are prescribed to help increase levels of norepinephrine and dopamine. Atomoxetine (Strattera) is a selective norepinephrine reuptake inhibitor, and is a unique ADHD medication, as it affects only norepinephrine, rather than dopamine. As a result, Strattera has a lower abuse potential. However, it may not be as effective as the psychostimulants are with many people with ADHD. Consulting with a physician is needed to find the appropriate medication and dosage. (Other SNRIs, currently approved as antidepressants, have also been used off-label for treatment of ADHD.)

    Depression

    Differences in the norepinephrine system are implicated in depression
    Clinical depression
    Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...

    . Serotonin-norepinephrine reuptake inhibitor
    Serotonin-norepinephrine reuptake inhibitor
    Serotonin–norepinephrine reuptake inhibitors are a class of antidepressant drugs used in the treatment of major depression and other mood disorders...

    s are antidepressants that treat depression by increasing the amount of serotonin
    Serotonin
    Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

     and norepinephrine available to postsynaptic cells in the brain. There is some recent evidence implying that SNRI
    SNRI
    SNRI may refer to:* Serotonin–norepinephrine reuptake inhibitor* Strategic Naval Research Institute...

    s may also increase dopamine
    Dopamine
    Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

     transmission. This is because SNRI
    SNRI
    SNRI may refer to:* Serotonin–norepinephrine reuptake inhibitor* Strategic Naval Research Institute...

    s work by inhibiting reuptake, i.e. preventing the serotonin
    Serotonin
    Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

     and norepinephrine transporters from taking their respective neurotransmitter
    Neurotransmitter
    Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

    s back to their storage vesicles
    Synaptic vesicle
    In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...

     for later use. If the norepinephrine transporter
    Norepinephrine transporter
    The norepinephrine transporter , also known as solute carrier family 6 member 2 , is a protein that in humans is encoded by the SLC6A2 gene....

     normally recycles some dopamine
    Dopamine
    Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

     too, then SNRI
    SNRI
    SNRI may refer to:* Serotonin–norepinephrine reuptake inhibitor* Strategic Naval Research Institute...

    s will also enhance dopaminergic
    Dopaminergic
    Dopaminergic means related to the neurotransmitter dopamine. For example, certain proteins such as the dopamine transporter , vesicular monoamine transporter 2 , and dopamine receptors can be classified as dopaminergic, and neurons which synthesize or contain dopamine and synapses with dopamine...

     transmission. Therefore, the antidepressant
    Antidepressant
    An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...

     effects associated with increasing norepinephrine levels may also be partly or largely due to the concurrent increase in dopamine
    Dopamine
    Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

     (in particular in the prefrontal cortex
    Prefrontal cortex
    The prefrontal cortex is the anterior part of the frontal lobes of the brain, lying in front of the motor and premotor areas.This brain region has been implicated in planning complex cognitive behaviors, personality expression, decision making and moderating correct social behavior...

     of the brain).

    Tricyclic antidepressant
    Tricyclic antidepressant
    Tricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms...

    s (TCAs) increase norepinephrine activity as well. Most of them also increase serotonin
    Serotonin
    Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

     activity, but tend to produce unwanted side-effects due to the nonspecific inactivation of histamine
    Histamine
    Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...

    , acetylcholine
    Acetylcholine
    The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...

    , and alpha-1 adrenergic
    Alpha-1 adrenergic receptor
    The alpha-1 adrenergic receptor is a G protein-coupled receptor associated with the Gq heterotrimeric G-protein. It consists of three highly homologous subtypes, including α1A-, α1B-, and α1D-adrenergic...

     receptors. Common side-effects include sedation, dry mouth, constipation, sinus tachycardia, memory impairment, orthostatic hypotension, blurred vision, and weight gain. For this reason, they have largely been replaced by newer selective reuptake drugs. These include the SSRI
    Selective serotonin reuptake inhibitor
    Selective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. The efficacy of SSRIs is disputed...

    s, e.g. fluoxetine
    Fluoxetine
    Fluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company...

     (Prozac), which however have little or no effect on norepinephrine, and the newer SNRI
    SNRI
    SNRI may refer to:* Serotonin–norepinephrine reuptake inhibitor* Strategic Naval Research Institute...

    s described above, such as venlafaxine
    Venlafaxine
    Venlafaxine is an antidepressant of the serotonin-norepinephrine reuptake inhibitor class. First introduced by Wyeth in 1993, now marketed by Pfizer, it is licensed for the treatment of major depressive disorder , as a treatment for generalized anxiety disorder, and comorbid indications in...

     (Effexor) and duloxetine
    Duloxetine
    Duloxetine is a serotonin-norepinephrine reuptake inhibitor manufactured and marketed by Eli Lilly. It is effective for major depressive disorder and has been shown to be as effective as venlafaxine for generalized anxiety disorder...

     (Cymbalta).

    Schizophrenia

    A commonly-known side-effect associated with schizo-affective patients known as akathisia
    Akathisia
    Akathisia, or acathisia, is a syndrome characterized by unpleasant sensations of inner restlessness that manifests itself with an inability to sit still or remain motionless...

     (commonly mistaken for schizophrenic symptoms) was found to be associated with increased levels of norepinephrine. Data supports the efficacy of novel antipsychotics that deal with agonism of the NMDA glutamate receptors, associated with regulating uptake of norepinephrine, which in turn affects the trafficking of glutamate. This suggests that schizophrenia may in fact have a greater association with abnormal norepinephrine-reuptake kinetics and less with dopamine, which may actually be responsible for a large part of the mechanism of glutamate release.

    Hypotension

    Norepinephrine is also used as a vasopressor medication (for example, brand name Levophed) for patients with critical hypotension
    Hypotension
    In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...

    . It is given intravenously and acts on both α1 and α2 adrenergic receptors to cause vasoconstriction. Its effects are often limited to the increasing of blood pressure through agonist activity on α1 and α2 receptors, and causing a resultant increase in peripheral vascular resistance. At high doses, and especially when it is combined with other vasopressors, it can lead to limb ischemia
    Ischemia
    In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...

     and limb death. Norepinephrine is used mainly to treat patients in vasodilatory shock states such as septic shock
    Septic shock
    Septic shock is a medical emergency caused by decreased tissue perfusion and oxygen delivery as a result of severe infection and sepsis, though the microbe may be systemic or localized to a particular site. It can cause multiple organ dysfunction syndrome and death...

     and neurogenic shock
    Neurogenic shock
    Neurogenic shock is a distributive type of shock resulting in hypotension, occasionally with bradycardia, that is attributed to the disruption of the autonomic pathways within the spinal cord. Hypotension occurs due to decreased systemic vascular resistance resulting in pooling of blood within the...

    , while showing fewer averse side-effects compared to dopamine
    Dopamine
    Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

     treatment.

    By site of action

    Different medication
    Medication
    A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...

    s affecting norepinephrine function have their targets at different points in the mechanism, from synthesis to signal termination.

    Synthesis modulators

    α-Methyltyrosine is a substance that intervenes in norepinephrine synthesis by substituting tyrosine for tyrosine hydroxylase
    Tyrosine hydroxylase
    Tyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to dihydroxyphenylalanine . It does so using tetrahydrobiopterin as a coenzyme. DOPA is a precursor for dopamine, which, in turn, is a precursor for norepinephrine ...

    , and blocking this enzyme.

    Vesicular transport modulators

    This transportation can be inhibited by reserpine
    Reserpine
    Reserpine is an indole alkaloid antipsychotic and antihypertensive drug that has been used for the control of high blood pressure and for the relief of psychotic symptoms, although because of the development of better drugs for these purposes and because of its numerous side-effects, it is rarely...

     and tetrabenazine
    Tetrabenazine
    Tetrabenazine is a drug for the symptomatic treatment of hyperkinetic movement disorder and is marketed under the trade names Nitoman in Canada and Xenazine in New Zealand and some parts of Europe, and is also available in the USA as an orphan drug. On August 15, 2008 the U.S...

    .

    Release modulators

    Inhibitors of norepinephrine release
    Substance Receptor
    acetylcholine
    Acetylcholine
    The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...

     
    muscarinic receptor
    norepinephrine (itself)/epinephrine
    Epinephrine
    Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...

     
    α2 receptor
    5-HT  5-HT receptor
    5-HT receptor
    The serotonin receptors, also known as 5-hydroxytryptamine receptors or 5-HT receptors, are a group of G protein-coupled receptors and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neurotransmission...

    adenosine  P1 receptor
    PGE
    Prostaglandin E
    Prostaglandin E is a family of naturally occurring prostaglandins and may be used pharmaceutically in medicine.Types include:* Prostaglandin E1 also termed Alprostadil* Prostaglandin E2 also termed DinoprostoneIt is created from prostaglandin E synthase....

     
    EP receptor
    histamine
    Histamine
    Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...

     
    H2 receptor
    H2 receptor
    H2 receptors are positively coupled to adenylate cyclase via Gs. It is a potent stimulant of cAMP production. It increases the intracellular Ca2+ concentrations and release Ca2+ from intracellular stores...

    enkephalin
    Enkephalin
    An enkephalin is a pentapeptide involved in regulating nociception in the body. The enkephalins are termed endogenous ligands, or specifically endorphins, as they are internally derived and bind to the body's opioid receptors. Discovered in 1975, two forms of enkephalin were revealed, one...

     
    δ receptor
    Delta Opioid receptor
    The δ-opioid receptors, also known as delta opioid receptor or simply delta receptor, abbreviated DOR, is an opioid receptor that has enkephalins as its endogenous ligands.-Function:...

    dopamine
    Dopamine
    Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

     
    D2 receptor
    ATP
    Adenosine triphosphate
    Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

     
    P2 receptor
    P2 receptor
    P2 receptor may refer to:*P2Y receptors*P2X receptorsP is for purinergic, P2 refers to ATP receptors, as opposed to P1 adenosine adenosine receptors. P2X receptors are ATP activated channels that allows the passage of ions across cell membranes. P2Y receptors are ATP activated G protein-coupled...


    Stimulators of norepinephrine release
    Substance Receptor
    adrenaline  β2 receptor
    angiotensin II  AT1 receptor

    Receptor binding modulators

    Examples include alpha blockers for the α-receptors, and beta blocker
    Beta blocker
    Beta blockers or beta-adrenergic blocking agents, beta-adrenergic antagonists, beta-adrenoreceptor antagonists or beta antagonists, are a class of drugs used for various indications. They are particularly for the management of cardiac arrhythmias, cardioprotection after myocardial infarction ,...

    s for the β-receptors.
    Uptake modulators

    Inhibitors of uptake 1 include:
    • cocaine
      Cocaine
      Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...

    • tricyclic antidepressant
      Tricyclic antidepressant
      Tricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms...

      s
      • desipramine
        Desipramine
        Desipramine is a tricyclic antidepressant . It inhibits the reuptake of norepinephrine and to a lesser extent serotonin. It is used to treat depression, but not considered a first line treatment since the introduction of SSRI antidepressants...

    • phenoxybenzamine
      Phenoxybenzamine
      Phenoxybenzamine is a non-selective, irreversible alpha antagonist.-Uses:It is used in the treatment of hypertension, and specifically that caused by pheochromocytoma...

    • amphetamine
      Amphetamine
      Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...



    Inhibitors of uptake 2 include:
    • normetanephrine
      Normetanephrine
      Normetanephrine is a metabolite of norepinephrine created by action of catechol-O-methyl transferase on norepinephrine. It is excreted in the urine and found in certain tissues. It is a marker for catecholamine-secreting tumors such as pheochromocytoma....

    • steroid hormone
      Steroid hormone
      A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens...

      s
    • phenoxybenzamine
      Phenoxybenzamine
      Phenoxybenzamine is a non-selective, irreversible alpha antagonist.-Uses:It is used in the treatment of hypertension, and specifically that caused by pheochromocytoma...


    Anti-Inflammatory agent role in Alzheimer’s Disease

    The norepinephrine from locus ceruleus cells in addition to its neurotransmitter role locally diffuses from "varicosities". As such, it provides an endogenous anti-inflammatory
    Anti-inflammatory
    Anti-inflammatory refers to the property of a substance or treatment that reduces inflammation. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids, which affect the central nervous system....

     agent in the microenvironment around the neurons, glial cell
    Glial cell
    Glial cells, sometimes called neuroglia or simply glia , are non-neuronal cells that maintain homeostasis, form myelin, and provide support and protection for neurons in the brain, and for neurons in other parts of the nervous system such as in the autonomous nervous system...

    s, and blood vessels in the neocortex and hippocampus. Up to 70% of norepinephrine projecting cells are lost in Alzheimer’s Disease. It has been shown that norepinephrine stimulates mouse microglia to suppress Aβ-induced production of cytokine
    Cytokine
    Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

    s and their phagocytosis of Aβ, suggesting this loss might have a role in causing this disease.

    Nutritional sources

    The synthesis of norepinephrine depends on the presence of tyrosine
    Tyrosine
    Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...

    , an amino acid found in proteins such as meat, nuts, and eggs. Dairy products such as cheese also contain high amounts of tyrosine (the amino acid is named for "tyros", the Greek word for cheese). However, the body can synthesise tyrosine from phenylalanine
    Phenylalanine
    Phenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...

    , an essential amino acid. Tyrosine is the precursor to dopamine
    Dopamine
    Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

    , which in turn is a precursor to epinephrine and norepinephrine.

    Serotonin
    Serotonin
    Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

    , a neurotransmitter that is in many ways the opposite of the catecholamine
    Catecholamine
    Catecholamines are molecules that have a catechol nucleus consisting of benzene with two hydroxyl side groups and a side-chain amine. They include dopamine, as well as the "fight-or-flight" hormones adrenaline and noradrenaline released by the adrenal medulla of the adrenal glands in response to...

    s, is also directly synthesized from an amino acid (tryptophan
    Tryptophan
    Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...

    ). However, tryptophan has a somewhat different process of degradation. When serotonin is catabolized in the body, it does not break down into useful substrates in the way that dopamine is further degraded into epinephrine
    Epinephrine
    Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...

     and norepinephrine. Instead, it breaks down into 5-hydroxyindoleacetic acid (5-HIA), an organic acid that may be harmful in high amounts. Tryptophan can further be catabolized into kynurenate, quinolinate, and picolinate, harmful substances that are generally regarded as markers of bodily inflammation.

    See also

    • Norepinephrine bitartrate
    • Catecholaminergic polymorphic ventricular tachycardia
      Catecholaminergic polymorphic ventricular tachycardia
      Catecholaminergic Polymorphic Ventricular Tachycardia is an electrophysiological disorder of the heart that occurs in genetically predisposed individuals...


    External links

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