Norepinephrine

neurotransmitters

Norepinephrine [nawr-ep-uh-nef-rin] is a hormone and a neurotransmitter. 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 favored nomenclature.

One of the most important functions of norepinephrine is its role as the neurotransmitter released from the sympathetic neurons (part of the subconscious, autonomic nervous system) affecting the heart. An increase in norepinephrine from the sympathetic nervous system increases the rate of contractions. As a stress hormone, norepinephrine affects parts of the brain, such as the amygdala, where attention and responses are controlled.

Along with epinephrine, norepinephrine also underlies the fight-or-flight response, directly increasing heart rate, triggering the release of glucose from energy stores, and increasing blood flow to skeletal muscle. It increases the brain’s oxygen supply. Norepinephrine can also suppress neuroinflammation when released diffusely in the brain from the brain stem.

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.  Norepinephrine, along with dopamine, has come to be recognized as playing a large role in attention and focus. For people with ADHD, psychostimulant medications such as methylphenidate (Ritalin/Concerta), dextroamphetamine (Dexedrine), and Adderall 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 who have ADHD.

Differences in the norepinephrine system are implicated in depression. Serotonin-norepinephrine reuptake inhibitors are antidepressants that treat depression by increasing the amount of serotonin and norepinephrine available to cells in the brain. There is some recent evidence implying that SNRIs may also increase dopamine transmission. This is because SNRIs work by inhibiting reuptake, i.e. preventing the serotonin and norepinephrine transporters from taking their respective neurotransmitters back to their storage vesicles for later use. If the norepinephrine transporter normally recycles some dopamine too, then SNRIs will also enhance dopaminergic transmission. Therefore, the antidepressant effects associated with increasing norepinephrine levels may also be partly or largely due to the concurrent increase in dopamine (particularly in the prefrontal cortex of the brain).

Tricyclic antidepressants (TCAs) increase norepinephrine activity as well. Most of them also increase serotonin activity, but tend to produce unwanted side effects including sedation, constipation, memory impairment, blurred vision, and weight gain. For this reason, they have largely been replaced by newer selective reuptake drugs. These include the SSRIs, e.g. fluoxetine (Prozac), which however have little or no effect on norepinephrine, and the newer SNRIs described above, such as venlafaxine (Effexor) and duloxetine (Cymbalta).

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