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Attention-Deficit/Hyperactivity Disorder Norepinephrine, along with dopamine, has come to be recognized as playing a large role in attention and focus. For people with ADD/ADHD, psychostimulant medications such as Ritalin/Concerta (methylphenidate), Dexedrine (dextroamphetamine), and Adderall (a non-racemic mixture of amphetamine salts) are prescribed to help increase levels of norepinephrine and dopamine. Strattera (atomoxetine) is a selective norepinephrine reuptake inhibitor (NRI), and is a unique ADD/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 ADD/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 ADD/ADHD.) Depression Differences in the norepinephrine system are implicated in depression. Serotonin-norepinephrine reuptake inhibitors (SNRIs) are antidepressants that treat depression by increasing the amount of serotonin and norepinephrine available to postsynaptic cells in the brain. There is some recent evidence showing that the norepinephrine transporter also transports some dopamine as well, 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). Some other antidepressants (for example, some tricyclic antidepressants (TCAs)) affect norepinephrine as well, in some cases without affecting other neurotransmitters (at least not directly). Vasopression Norepinephrine is also used as a vasopressor medication (for example, brand name Levophed) for patients with critial hypotension. It is given intravenously and acts on both alpha-1 adrenergic receptors to cause vasoconstriction and beta-1 adrenergic receptors to increase heart rate, stroke volume and cardiac output. The net effect is to increase blood pressure. Norepinephrine is mainly used to treat patients in septic shock and has shown a survival benefit over dopamine. Biosynthesis Norepinephrine is synthesized by a series of enzymatic steps in the adrenal medulla from the amino acid tyrosine. The first reaction is the oxidation into dihydroxyphenylalanine (L-DOPA), followed by decarboxylation into the neurotransmitter dopamine, and the final β-oxidation into norepinephrine. Norepinephrine can be further methylated by phenylethanolamnine N-methyltransferase to epinephrine (called adrenaline outside the USA). Metabolites In mammals, norepinephrine is rapidly degraded to various metabolites. The principle metabolites are: | ||||||||||
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