Norepinephrine is an important chemical messenger in the nervous system. It regulates affective states, learning and memory, hormone and autonomic functions.
What is Norepinephrine?
Norepinephrine (NE) also called Noradrenaline (NA) or Noradrenalin is a neurotransmitter that functions in the human brain and body as a hormone and neurotransmitter (R).
A neurotransmitter is a chemical that is released from neurons.
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 urination and slows the gut flow.
It is released from the sympathetic nervous system in response to stress. Because the release of norepinephrine affects other organs of the body, it is also referred to as a “stress hormone” (R).
It is released by the inner layer of the adrenal glands, two walnut-sized structures that sit on top of your kidneys.
Here’s how the body creates norepinephrine:
Broadly speaking, the effect of norepinephrine on each target organ is to modify its state in a way that makes it more conducive to active body movement, often at a cost of increased energy use and increased wear and tear (R).
This can be contrasted with the acetylcholine-mediated effects of the parasympathetic nervous system, which modifies most of the same organs into a state more conducive to rest, recovery, and digestion of food, and usually less costly in terms of energy expenditure (R).
The effects of norepinephrine include (R):
- In the eyes, an increase in production of tears, making the eyes moister, and pupil dilation.
- In the heart, an increase in the amount of blood pumped.
- In brown adipose tissue, an increase in calories burned to generate body heat.
- In the arteries, constriction of blood vessels, causing an increase in blood pressure.
- In the kidneys, a release of renin and retention of sodium in the bloodstream.
- In the liver, an increase in production of glucose, either by glycogenolysis after a meal or by gluconeogenesis when food has not recently been consumed.
- In skeletal muscles, an increase in glucose uptake.
- In fat cells, an increase in fat burning.
- In the stomach and intestines, a reduction in digestive activity. This results from an inhibitory effect of norepinephrine on the intestinal nervous system, causing decreases in gastrointestinal mobility, blood flow, and secretion of digestive substances.
Benefits of Norepinephrine
1) Norepinephrine Helps Depression and Mood
Preliminary studies with NE and Serotonin reuptake inhibitors suggest that they significantly improve social functioning in patients with depression (R).
Therapeutic agents which specifically increase NE activity are effective antidepressants, and those acting simultaneously on 5-HT (serotonin) and NE neurotransmission may have an antidepressant action superior to SSRIs (R).
NE affects the behaviors of individuals including a modulation of vigilance, arousal, attention, motivation, reward and also learning and memory (R).
2) Norepinephrine Plays A Role In Memory and Cognitive Function
Norepinephrine released by the locus coeruleus affects brain function in a number of ways.
It enhances processing of sensory inputs, enhances attention, enhances formation and retrieval of both long-term and working memory, and enhances the ability of the brain to respond to inputs by changing the activity pattern in the prefrontal cortex and other areas (R).
Retrieval is an important step in memory processes during which norepinephrine appears to act.
This retention deficit was rescued by the injection of a precursor of norepinephrine before the test, demonstrating that norepinephrine is necessary for the access to a memory and is important for consolidation and retrieval of some types of memory (R1, R2).
NE is involved in the neurophysiology and the clinical features of cerebral aging and cognitive function slowing down, loss of behavioral adjustment (R).
3) Norepinephrine May Help Alzheimer’s Disease
Loss of norepinephrine (NE) releasing neurons, in the locus coeruleus of the brainstem, occurs in Alzheimer’s Disease (AD) (R).
NE reverses the effects and slows neurodegeneration in animal models, raising the possibility that treatments which increase NE transmission have the potential to reverse or delay AD-related pathology (R1, R2).
4) Norepinephrine Help ADHD
Lower dopamine and norepinephrine are responsible for the clinical manifestations of ADHD (Attention Deficit Hyperactivity Disorder).
Pharmacologic agents that are selective for NE have been effective in treating ADHD (R).
Specific norepinephrine reuptake inhibitors are one of the non-stimulants used in the treatment for ADHD (R).
5) Norepinephrine May Help Parkinson’s Disease
Tissues concentrations of NE are markedly decreased in various regions of the Parkinson’s Disease (PD) brain (R). In several regions, NE content is reduced to less than half of its usual tissue concentration (R).
Also, actions of NE are involved in one or more mechanisms linked to neurodegeneration in the Parkinson’s brain (R).
6) Norepinephrine May Help Chronic Fatigue Syndrome
People with chronic fatigue syndrome have low norepinephrine levels upon exercising (R).
7) Norepinephrine May Help Bipolar
People with bipolar have lower levels of norepinephrine (R).
8) Norepinephrine May Alleviate Migraines
People with debilitating migraine headaches have lower norepinephrine when lying down (R).
Negatives of Norepinephrine
Chronic stress, if continued for a long time, can damage many parts of the body.
A significant part of the damage is due to the effects of sustained norepinephrine release, because of norepinephrine’s general function of directing resources away from maintenance, regeneration, and reproduction, and toward systems that are required for active movement.
The consequences can include slowing of growth (in children), sleeplessness, loss of libido, gastrointestinal problems, impaired disease resistance, slower rates of injury healing, depression, and increased vulnerability to addiction (R).
1) Norepinephrine Increases Heart Rate and Blood Pressure
Noradrenaline can increase atrial and ventricular contractile force through beta-2 adrenoreceptors but only at high concentrations (R).
Treatment with low doses of NE resulted in a marked increase in systolic but not diastolic arterial blood pressure in rat hearts (R).
2) Norepinephrine Affects Glucose Transport
Noradrenaline stimulates glucose transport in brown fat cells by enhancing the functional activity of GLUT1 (R).
The breakdown of glycogen is also activated by NE as a result of an increase in 3,5-cyclic AMP (R).
Genetics of Norepinephrine
Dopamine beta-hydroxylase converts dopamine to norepinephrine. There are a variety of SNPs in SelfDecode that can harm the conversion and lower norepinephrine.
SelfDecode is an app that can help you decipher your biology and help you understand why some things work for you, while others don’t.
- Exercise (R)
- Cold Exposure (R)
- Phenylalanine (precursor)
- Tyrosine (precursor)
- Mucuna (contains L-Dopa)
- Acetyl L-Carnitine (R)
- Nicotine (R, R, R)
- Bitter orange (with Rhodiola) (R)
- Rhodiola (with bitter orange) (R) (inhibits MAOA and COMT)
- Sodium reduction (R)
- Tianeptine (R)
- EGCG (MAO and COMT inhibitor)
- Quercetin (inhibits MAOA and COMT)
- Fisetin (inhibits MAOA and COMT)
- Noradrenergic receptors include alpha(α)1, alpha(α)2 and beta (β)-adrenergic subtypes (R).
- NE is released in the entire brain areas with the exception of the basal ganglia, from the locus coeruleus (LC), the bilateral small nuclei located in the dorsal tegmentum (R).
- Noradrenaline is very effective in raising arterial blood pressure and, under almost all circumstances, can be titrated to achieve the desired MAP in a given patient. However, since noradrenaline induces vasoconstriction via α-adrenergic stimulation, it may also decrease organ blood flow, if regional vascular beds constrict in excess (R).
- Norepinephrine increases the liver mitochondrial complex I-dependent and II-dependent respiratory control ratios. This effect is probably mediated by a direct effect of norepinephrine on liver cells (R).
- Inhibition of dopamine-β-hydroxylase in the mouse caused a decrease in motor activity, depletion of brain noradrenaline (NA) and reduction in body temperature. The data support the view that central NA neurons are involved in the control of motor activity and body temperature in the mouse (R)