Phenylpropanolamine, also known as the stereoisomers norephedrine and
norpseudoephedrine, is a psychoactive drug of the phenethylamine and
amphetamine chemical classes which is used as a stimulant, decongestant, and
anorectic agent. It is commonly used in prescription and over-the-counter cough
and cold preparations. In veterinary medicine, it is used to control urinary
incontinence in dogs under trade names Propalin and Proin.
In the United States, PPA is no longer sold due to a proposed increased risk of
stroke in younger women. In a few countries in Europe, however, it is
still available either by prescription or sometimes over-the-counter. In
Canada, it was withdrawn from the market on 31 May 2001. In India human use of
PPA and its formulations was banned on 10 February 2011, but the ban was
overturned by the court in September 2011.
Pharmacology Phenylpropanolamine acts as an
alpha-adrenergic receptor and beta-adrenergic receptor agonist as well
as a dopamine receptor D1 partial agonist.
Many sympathetic hormones and neurotransmitters are based on the
phenethylamine skeleton, and function generally in "fight or flight" type
responses, such as increasing heart rate, blood pressure, dilating the
pupils, increased energy, drying of mucous membranes, increased sweating,
and a significant number of additional effects.
Legal status In Europe, PPA is still available in
prescription decongestants such as Rinexin, as well as over-the-counter
medications such as Wick DayMed. In the United Kingdom, PPA was available
in many 'all in one' cough and cold medications which usually also feature
paracetamol or another analgesic and caffeine and could also be purchased on
its own; however, it is no longer approved for human use. As of 11 August,
a European Category 1 Licence is required to purchase PPA for academic
use. In the United States, the Food and Drug
Administration issued a public health advisory against the use of the drug in
November 2000. In this advisory, the FDA requested that all drug companies
discontinue marketing products containing PPA. The agency estimates
that PPA caused between 200 and 500 strokes per year among 18-to-49-year-old
users. In 2005, the FDA removed PPA from over-the-counter sale. Because of its
potential use in amphetamine manufacture, it is controlled by the
Combat Methamphetamine Epidemic Act of 2005. It is still available for
veterinary use in dogs, however, as a treatment for urinary incontinence.
Internationally, an item on the agenda of the 2000 Commission on Narcotic Drugs
session called for including the stereoisomer norephedrine in Table I of
United Nations Convention Against Illicit Traffic in Narcotic Drugs and
Psychotropic Substances. Drugs containing PPA were banned in
India on 27 January 2011. On 13 September 2011 Madras High Court revoked
a ban on manufacture and sale of paediatric drugs nimesulide and
phenylpropanolamine. Chemistry
There are four optical isomers of PPA: dextro- and levo- nor ephedrine, and
dextro- and levo- nor pseudoephedrine. d-Norpseudoephedrine is also known as
cathine, and occurs naturally in Catha edulis.
Phenylpropanolamine, structurally, is in the phenethylamine family, consisting of
a cyclic benzene or phenyl group, a two carbon ethyl moiety, and a terminal
nitrogen, hence the name phen-ethyl-amine. The methyl group on
the alpha carbon also makes this compound a member of the amphetamine
family. Ephedrine is the N-methyl analogue of phenylpropanolamine.
Exogenous compounds in this family are degraded too rapidly by monoamine
oxidase to be active at all but the highest doses. However, the addition of
the α-methyl group allows the compound to avoid metabolism and confer an
effect. In general, N-methylation of primary amines increases their potency;
whereas β-hydroxylation decreases CNS activity, but conveys more selectivity
for adrenergic receptors. See also
Amphetamine Ephedrine
Methamphetamine Pseudoephedrine
Substituted amphetamine Notes
References Hartung, W. H.; Munch, J. C.. "Amino
Alcohols. I. Phenylpropanolamine and Para-Tolylpropanolamine". Journal of the
American Chemical Society 51: 2262. doi:10.1021/ja01382a044.
Hartung, W. H.; Chang, Y. T.. "Palladium Catalysis. IV.1Change in the Behavior of
Palladium-on-Charcoal in Hydrogenation Reactions2". Journal of the American
Chemical Society 74: 5927. doi:10.1021/ja01143a031.
W. N. Nagai, S. Kanao, Ann. Chem., 470, 157.
G. Wilbert, P. Sosis, U.S. Patent 3,028,429.
External links Phenylpropanolamine Information Page at
FDA.gov U.S. National Library of Medicine: Drug
Information Portal – Phenylpropanolamine