Phenylpropanolamine

Phenylpropanolamine

185px
Systematic (IUPAC) name
(1R,2S)-2-amino-1-phenylpropan-1-ol
Clinical data
Routes of administration	Oral
Legal status
Legal status	UK: General sales list (GSL, OTC) US: ℞-only ℞ (Prescription only)
Pharmacokinetic data
Biological half-life	2.1 to 3.4 hours.
Identifiers
CAS Number	14838-15-4
ATC code	R01BA01 (WHO)
PubChem	CID 26934
DrugBank	APRD00457
ChemSpider	25082
Chemical data
Formula	C9H13NO
Molar mass	151.206 g/mol[[]]
(verify)

Phenylpropanolamine (PPA; Accutrim), also known as norephedrine and oxyamphetamine, 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 without a prescription due to a proposed increased risk of stroke in younger women. In Europe, however, it is still available by both prescription and over-the-counter. In Canada, it was withdrawn from the market on May 31, 2001.

Pharmacology

PPA acts as a potent and selective releasing agent of norepinephrine and epinephrine, or as a norepinephrine releasing agent (NRA). It also acts as a dopamine releasing agent (DRA) to a lesser extent.

Chemistry

There are four optical isomers of PPA: dextro- and levo- norephedrine, and dextro- and levo- norpseudoephedrine. d-Norpseudoephedrine is also known as cathine, and occurs naturally in Catha edulis ("Khat").

Just as ephedrine can be chemically reduced into methamphetamine, PPA may be chemically reduced into amphetamine. Structurally, PPA is to ephedrine, just as amphetamine is to methamphetamine, and as cathinone is to methcathinone. PPA can also be used in the synthesis of phenmetrazine and 4-methylaminorex.

Synthesis is a standard Henry reaction between benzaldehyde and nitroethane, although care is taken not to dehydrate the alcohol. Reduction is usually done with a mild agent including zinc. The products of this step can be vacuum distilled.

Side Effects

A scientific study found an increased risk of hemorrhagic stroke in women who used PPA, although it is not clear which isomer is to blame. A study at the Yale University School of Medicine in 1999 had produced similar results.[1] Reports of cases of hemorrhagic strokes in PPA users had been circulating since the 1970s.

A report from the Dept. of Psychiatry, F. Edward Hebert School of Medicine, Bethesda, Maryland in Pharmacopsychiatry states:

We have reviewed 37 cases (published in North America and Europe since 1960) that received diagnoses of acute mania, paranoid schizophrenia, and organic psychosis and that were attributed to PPA product ingestion. Of the 27 North American case reports, more reactions followed the ingestion of combination products than preparations containing PPA alone; more occurred after ingestion of over-the-counter products than those obtained by prescription or on-the-street; and more of the cases followed ingestion of recommended doses than overdoses.
Failure to recognize PPA as an etiological agent in the onset of symptoms usually led to a diagnosis of schizophrenia or mania, lengthy hospitalization, and treatment with substantial doses of neuroleptics or lithium.

Detection of use

Phenylpropanolamine may be quantitated in blood, plasma or urine to confirm a diagnosis of poisoning or assist in a medicolegal death investigation. Many commercial immunoassay screening tests directed at the amphetamines cross-react appreciably with phenylpropanolamine, but chromatographic techniques can easily distinguish phenylpropanolamine from other phenethylamine derivatives. Blood or plasma phenylpropanolamine concentrations are typically in the 50-300 µg/L range in persons taking the drug therapeutically, 300-3000 µg/L in abusers or poisoned patients and 2–50 mg/L in cases of acute fatal overdosage.

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 is available in many 'all in one' cough and cold medications which usually also feature paracetamol or another analgesic and caffeine. It can also be purchased on its own. It is classed as GSL (general sale license) and is completely derestricted, therefore saleable by any shop.

In the United States, the Food and Drug Administration (FDA) 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 PPA in Table I of United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances

PPA is available in India in the form of a combination tablet with cetirizine as Alerid-D, which is manufactured by Cipla. It is also present in popular cold and flu treatment medicine D-Cold Total available over the counter.

See also

• Phenethylamine
• Cathine
• Cathinone
• Methcathinone
• Ephedrine
• Pseudoephedrine
• Amphetamine
• Methamphetamine
• Phenmetrazine
• 4-Methylaminorex

External links

• Phenylpropanolamine Information Page at www.FDA.gov
• A Dose of Denial: How drug makers sought to keep popular cold and diet remedies on store shelves after their own study linked them to strokes. By Kevin Sack and Alicia Mundy.Los Angeles Times, March 28, 2004.
• Doubt Is Their Product by David Michaels, Scientific American, June 2005
• Phenylpropanolamine by Richard Clapp, a case study at DefendingScience.org
• Widely Circulated Email About Phenylpropanolamine Description of widely circulated email using out-of-date information about Phenylpropanolamine.
• Treatment of urethral sphincter mechanism incompetence in 11 bitches with a sustained-release formulation of phenylpropanolamine hydrochloride Use of Phenylpropanolamine in dogs.
• U.S. National Library of Medicine: Drug Information Portal - Phenylpropanolamine

ca:Fenilpropanolamina zh:苯丙醇胺