Chemical Properties
solid
Uses
An adrenergic neurotransmitter.
Uses
Vascular active drug resistance to shock
Uses
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.
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
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].
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.]
