norepinefrine

Norepinefrine, also known as norepinephrine or noradrenaline, is a catecholamine that functions as both a neurotransmitter in the central nervous system and a circulating hormone in the peripheral nervous system. It is synthesized from the amino acid tyrosine through sequential enzymatic steps to L-DOPA and dopamine, with the final step catalyzed by dopamine beta-hydroxylase. In the brain, norepinephrine is produced primarily by neurons in the locus coeruleus and projected widely. In the adrenal medulla, chromaffin cells release norepinephrine along with epinephrine into the bloodstream.

Its effects are mediated by adrenergic receptors, primarily alpha1, alpha2, and beta1, with beta2 having a lesser role for norepinephrine. Peripheral actions include increased heart rate and contractility (beta1), vasoconstriction and increased peripheral vascular resistance (alpha1), and modulation of insulin release. The net effect is typically an increase in blood pressure and alertness during the fight-or-flight response. In the brain, norepinephrine modulates arousal, attention, mood, and learning.

Norepinephrine is released by sympathetic nerve terminals through calcium-dependent exocytosis and is taken up again primarily via the norepinephrine transporter. It is inactivated by monoamine oxidase and catechol-O-methyltransferase and metabolized to vanillylmandelic acid and other metabolites excreted in urine.

Medically, norepinephrine is used as a vasopressor to raise blood pressure in septic shock and other forms of shock. Side effects include hypertension, tachycardia, and reduced blood flow to certain organs. Dysregulation of noradrenergic signaling is implicated in various psychiatric and neurodegenerative conditions, and drugs that influence norepinephrine reuptake or release are used in treating attention-deficit/hyperactivity disorder and depression.