Pseudoephedrine

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Pseudoephedrine

Systematic (IUPAC) name
(R*,R*)-2-methylamino-1-phenylpropan-1-ol
Identifiers
CAS number	90-82-4
ATC code	R01BA02
PubChem	CID 7028
DrugBank	DB00852
ChemSpider	6761
Chemical data
Formula	C10H15NO
Mol. mass	165.23
Pharmacokinetic data
Bioavailability	~100%[1]
Metabolism	hepatic (10–30%)
Half-life	4.3-8 hours[1]
Excretion	43-96% renal[1]
Therapeutic considerations
Pregnancy cat.	B2(AU) C(US)
Legal status	Pharmacist Only (S3) (AU) P (UK)
Routes	oral
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Pseudoephedrine (PSE) [pronunciation: /ˌsuːdəʊɪˈfɛdɹɪn/ or /ˌsuːdoˈɛfədriːn/] is a sympathomimetic drug of the phenethylamine and amphetamine chemical classes. It is used as a nasal/sinus decongestant and stimulant, or as a wakefulness-promoting agent.

The salts pseudoephedrine hydrochloride and pseudoephedrine sulfate are found in many over-the-counter preparations either as a single ingredient or, more commonly, in combination with antihistamines, guaifenesin, dextromethorphan, paracetamol (acetaminophen), and/or NSAIDs (e.g., aspirin, ibuprofen, etc.).

Contents [show] 1 Chemistry 2 Nomenclature 3 Synthesis 4 Mechanism of action 5 Medical uses 5.1 Indications 5.2 Adverse effects 5.3 Precautions and contraindications 5.4 Common brand names 6 Alternative and illicit use 6.1 Sports 6.2 Detection of use 7 National legislation 7.1 Australia 7.2 Mexico 7.3 New Zealand 7.4 United Kingdom 7.5 United States 8 See also 9 References

[edit] Chemistry

Two pairs of enantiomers: Ephedrine (top) and Pseudoephedrine (bottom)

Pseudoephedrine is a diastereomer of ephedrine. Pseudoephedrine is a chiral molecule, meaning it occurs in both “left-handed” and “right-handed” configurations which are not superimposable.

Pseudoephedrine is a precursor of methamphetamine and methcathinone.

[edit] Nomenclature

The dextrorotary (+)- or d- enantiomer is (1S,2S)-Pseudoephedrine, whereas the levorotating (−)- or l- form is (1R,2R)-Pseudoephedrine.

In the outdated d/l system (+)-Pseudoephedrine is also referred to as l-Pseudoephedrine and (—)-Pseudoephedrine as d-Pseudoephedrine (in the Fisher projection then the phenylring is drawn at bottom). ^{[2] [3]}

Often the d/l system (with small caps) and the d/l system (with lower-case) are confused. The result is that the dextrorotary d-Pseudoephedrine is wrongly named d-Pseudoephedrine and the levorotary l-Ephedrine (the diastereomer) wrongly l-Ephedrine.

The IUPAC names of the two enantiomers are (1S,2S)- respectively (1R,2R)-2-methylamino-1-phenylpropan-1-ol. Synonyms for both are psi-Ephedrine and threo-Ephedrine.

Pseudoephedrine is the International Nonproprietary Name (INN) of the (+)-form, when used as pharmaceutical substance. ^[4]

[edit] Synthesis

Although pseudoephedrine occurs naturally as an alkaloid in certain plant species (for example, as a constituent of extracts from the ephedra species, also known as Ma Huang, in which it occurs together with other isomers of ephedrine), the majority of pseudoephedrine produced for commercial use is derived from yeast fermentation of dextrose in the presence of benzaldehyde. In this process, specialized strains of yeast (typically a variety of Candida utilis or Saccharomyces cerevisiae) are added to large vats containing water, dextrose and the enzyme pyruvate decarboxylase (such as found in beets and other plants). After the yeast has begun fermenting the dextrose, the benzaldehyde is added to the vats, and in this environment the yeast convert the ingredients to the precursor l-phenylacetylcarbinol (L-PAC). L-PAC is then chemically converted to pseudoephedrine via reductive amination.^[5]

The bulk of pseudoephedrine is produced by commercial pharmaceutical manufacturers in India and China, where economic and industrial conditions favor the mass production of pseudoephedrine for export.^[6]

[edit] Mechanism of action

Pseudoephedrine is a sympathomimetic amine. Its principal mechanism of action relies on its indirect action on the adrenergic receptor system. The vasoconstriction that pseudoephedrine produces is believed to be principally an α-adrenergic receptor response. ^[7]

While it may have weak or no direct agonist activity at α- and β-adrenergic receptors, the principal mechanism is to cause the release of endogenous norepinephrine (noradrenaline) from storage vesicles in presynaptic neurons. The displaced noradrenaline is released into the neuronal synapse where it is free to activate the postsynaptic adrenergic receptors. These adrenergic receptors are located on the muscles lining the walls of blood vessels. When activated by pseudoephedrine, the muscles contract, causing the blood vessels to constrict (vasoconstriction). The constricted blood vessels now allow less fluid to leave the blood vessels and enter the nose, throat and sinus linings, which results in decreased inflammation of nasal membranes as well as decreased mucus production. Thus, by constriction of blood vessels, mainly those located in the nasal passages, pseudoephedrine causes a decrease in the symptoms of nasal congestion.