Norepinephrine, known as noradrenaline outside the USA, is a catecholamine and a phenethylamine with chemical formula C8H11NO3. It is released from the adrenal glands as a hormone into the blood, but it is also a neurotransmitter in the nervous system where it is released from noradrenergic neurons during synaptic transmission. It is one of the 'stress hormones' and affects parts of the human brain where attention and impulsivity are controlled. Along with epinephrine this compound effects the fight-or-flight response, activating the sympathetic nervous system to directly increase heart rate, release energy from fat, and increase muscle readiness.
The host of physiological changes activated by a stressful event are unleashed in part by activation of a nucleus in the brain stem called the locus ceruleus. This nucleus is the origin of most norepinephrine pathways in the brain. Neurons using norepinephrine as their neurotransmitter project bilaterally from the locus ceruleus along distinct pathways to the cerebral cortex, limbic system, and the spinal cord, among other projections.
At synapses it acts on both alpha and beta adrenoreceptors.
Changes in the norepinephrine system are implicated in depression. SNRIs treat depression by increasing the amount of serotonin and norepinephrine available to postsynaptic cells in the brain. There is some recent evidence that norepinephrine autoreceptors may also reuptake dopamine, implying SNRIs may increase dopamine transmission as well.
Some other antidepressants (for example some Tricyclic antidepressants (TCAs)) affect norepinephrine as well, in some cases without affecting other neurotransmitters (at least not directly).
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 ?-oxidation into norepinephrine. Norepinephrine can be further methylated to epinephrine (called adrenaline outside the USA).
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