Norepinephrine

Toxicity

In high dose and especially when it is combined with other vasopressors, it can lead to limb ischemia and limb death.

Description

Norepinephrine is a natural compound in the catecholamine family that acts as a hormone and neurotransmitter. Its original name was noradrenaline, which is still used in the United Kingdom. The United States and the World Health Organization use norepinephrine. “Nor” in norepinephrine indicates that it has the structure of the parent molecule epinephrine with a hydrogen atom in place of the N-methyl group.
According to the Merck Index, norepinephrine “occurs in animals and [humans] and is a sympathomimetic hormone of both adrenal origin and adrenergic orthosympathetic postganglionic origin in [humans].” As an adrenal hormone, its release triggers vasoconstriction, which increases blood pressure. Despite its hazards (see table), this characteristic led scientists to develop norepinephrine as an intravenous drug for treating patients with very low blood pressure.
Physiologist Ulf van Euler at the Karolinska Institute (Solna, Sweden) discovered norepinephrine’s role in the body in 1945. He shared the 1970 Nobel Prize in Physiology or Medicine for his work on neurotransmitters.
Earlier this year, researchers reported a previously unknown property of norepinephrine. Ya-Chieh Hsu and colleagues at Harvard University (Cambridge, MA) and other research institutions used laboratory mice to determine the underlying biochemical cause of stress-induced hair depigmentation. They found that the culprit is norepinephrine, which is released by mammals’ adrenal glands when animals are under stress.
But the authors’ big surprise came when they removed the adrenal glands from mice to test their finding: The rodents still went gray. Undaunted, the researchers discovered that animals under stress also release norepinephrine from the sympathetic nervous system. The chemical reaches hair follicles and depletes them of pigment-producing stem cells.

Chemical properties

solid

The Uses of Norepinephrine

Norepinephrine is used for increasing cardiac constriction and for the necessary elevation of blood pressure after sharp decline, which can result from surgical intervention or trauma.

The Uses of Norepinephrine

Vascular active drug resistance to shock

The Uses of Norepinephrine

An adrenergic neurotransmitter.

Background

Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.

Indications

Mainly used to treat patients in vasodilatory shock states such as septic shock and neurogenic shock and has shown a survival benefit over dopamine. Also used as a vasopressor medication for patients with critical hypotension.

What are the applications of Application

L-Noradrenaline is an adrenergic neurotransmitter

Definition

ChEBI: The R-enantiomer of noradrenaline.

brand name

Levophed (Hospira);Noradrec;Xylotox.

World Health Organization (WHO)

Vasoconstrictor agents have been in use for many years to prolong duration of action of local anaesthetics, particularly in dentistry. Combination products containing epinephrine or levarterenol in concentrations of 1:80,000 or less remain widely available. See also WHO comment for epinephrine.

Biological Functions

Most central noradrenergic neurons are located in the nucleus locus ceruleus of the pons and in neurons of the reticular formation. Fibers from these nuclei innervate a large number of cortical, subcortical, and spinomedullary fields. Many functions have been ascribed to the central noradrenergic neurons, including a role in affective disorders (see Chapter 33), in learning and memory, and in sleep–wake cycle regulation.The mammalian CNS contains both α- and β-adrenoceptors.

General Description

Norepinephrine (NE, Levophed) differs from DA onlyby addition of a 1-OH substituent (β-OH-DA) and from Eonly by lacking the N-methyl group. Like DA, it is polar andrapidly metabolized by both COMT and MAO, resulting inpoor oral bioavailability and short DOA (1 or 2 minutes evenwhen given intravenously). It is a stimulant of α1-, α2-, andβ1-adrenoceptors (notice that lacking the N-methyl group resultsin lacking β2- and β3-activity). It is used to counteractvarious hypotensive crises, because its α-activity raisesblood pressure and as an adjunct treatment in cardiac arrestbecause its β-activity stimulates the heart. It has limitedclinical application caused by the nonselective nature of itsactivities.

Hazard

May cause local tissue necrosis, headache, bradycardia, hypertension; poison; teratogen; mutagen.

Biochem/physiol Actions

Adrenergic neurotransmitter

Pharmacokinetics

Noradrenaline acts on both alpha-1 and alpha-2 adrenergic receptors to cause vasoconstriction. Its effect in-vitro is often limited to the increasing of blood pressure through antagonising alpha-1 and alpha-2 receptors and causing a resultant increase in systemic vascular resistance.

Pharmacology

Norepinephrine is the primary neurotransmitter produced and released by adrenergic neurons, and in literature it is also described as and called () noradrenaline or levarterenol. This vasopressor catecholamine reduces both the resistance and capacity of blood vessels by stimulating α-adrenoreceptors and having a direct cardiostimulatory effect, which is accomplished by activation of β1-adrenoreceptors. Norepinephrine exhibits significantly less activity than epinephrine as a drug for widening blood vessels through the activation of β2-adrenoreceptors. Elevation of both stylistic and diastolic blood pressure is a typical reaction to intravenous introduction of norepinephrine.

Safety Profile

Poison by ingestion, intraperitoneal, subcutaneous, and intravenous routes. An experimental teratogen. Experimental reproductive effects. Human mutation data reported. A sympathomimetic vasopressor. When heated to decomposition it emits toxic fumes of NOx.

Synthesis

Norepinephrine, L-1-(3,4-dihydroxyphenyl)-2-aminoethanol (11.1.4), is synthesized by two methods starting from 3,4-dihydroxybenzaldehyde. According to the first method, the indicated aldehyde is transformed into the cyanohydrin (11.1.3) by reaction with hydrogen cyanide, which is then reduced into norepinephrine (11.1.5).

The second method consists of the condensation of diacetate of the same aldehyde with nitromethane, which forms (3,4-diacetoxyphenyl)-2-nitroethanol (11.1.5). Then the nitro group is reduced and the product (11.1.6) is hydrolyzed into the desired norepinephrine (11.1.4) [4,9,13,14].

Metabolism

Purification Methods

Recrystallise adrenor from EtOH and store it in the dark under N2. [pKa, Lewis Brit J Pharmacol Chemother 9 488 1954, UV: Bergstr.m et al. Acta Physiol Scand 20 101 1950, Fluorescence: Bowman et al. Science NY 122 32 1955, Tullar J Am Chem Soc 70 2067 1948.] The L-tartrate salt monohydrate has m 102-104.5o, [] D -11o (c 1.6, H2O), after recrystallisation from H2O or EtOH. [Beilstein 13 III 2382.]