Phenylpropanolamine

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Phenylpropanolamine
RS-Norephedrin
Phenylpropanolamine2.png
Systematic (IUPAC) name
2-amino-1-phenylpropan-1-ol
Clinical data
AHFS/Drugs.com Multum Consumer Information
Legal status Unknown (UK) ℞-only
Routes Oral
Pharmacokinetic data
Half-life 2.1 — 3.4 hours
Identifiers
CAS number 14838-15-4 YesY
ATC code R01BA01 QG04BX91
PubChem CID 10297
DrugBank DB00397
ChemSpider 9875 YesY
UNII 33RU150WUN YesY
KEGG D08368 YesY
ChEMBL CHEMBL136560 YesY
Chemical data
Formula C9H13NO 
Mol. mass 151.206 g/mol
 YesY (what is this?)  (verify)

Phenylpropanolamine (PPA; Accutrim; β-hydroxy amphetamine), 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.[1] 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 by either prescription or sometimes over-the-counter. In Canada, it was withdrawn from the market on 31 May 2001.[2] In India human use of PPA and its formulations were banned on 10 February 2011.[3]

Pharmacology[edit]

Phenylpropanolamine 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. It works by mimicking the effects of endogenous catecholamines such as epinephrine and norepinephrine, and to a lesser degree dopamine.

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.

The use of it has been shown to potentiate the effects of caffeine.

Legal status[edit]

In Europe, PPA is still available in prescription decongestants such as Rinexin,[4] 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 (FDA) issued a public health advisory[5] 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.[6] 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.[7]

Drugs containing PPA were banned in India on 27 January 2011.[8] On 13 September 2011 Madras High Court revoked a ban on manufacture and sale of paediatric drugs nimesulide and phenylpropanolamine (PPA).[9]

Chemistry[edit]

Space filling model of phenylpropanolamine

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 ("Khat").[10]

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 (the first carbon before the nitrogen group) also makes this compound a member of the amphetamine family.

Exogenous compounds in this family are degraded too rapidly to be active at a reasonable dose. However, the addition of the alpha methyl group allows the compound to avoid metabolism and confer an effect. Ephedrine is the N-methyl analogue of phenylpropanolamine. In general, N-methylation of phenethylamines confers greater stability by avoiding MAO degradation.

The beta hydroxyl group in general seems to convey more selectivity for norepinephrine and adrenergic receptors; however, the structure activity relationship is much more complex than this.

Phenylpropanolamine, D,L-erythro-1-phenyl-2-methylaminopropan-1-ol, is synthesized from propiophenone by nitrosation (with methyl nitrite) into an isonitroso derivative. Reduction of this by hydrogen in hydrochloric acid while simultaneously using two catalysts, palladium on carbon and platinum on carbon, gives norephedrine.

Phenylpropanolamine synthesis.png

See also[edit]

Notes[edit]

  1. ^ Flavahan NA (April 2005). "Phenylpropanolamine constricts mouse and human blood vessels by preferentially activating alpha2-adrenoceptors". J. Pharmacol. Exp. Ther. 313 (1): 432–9. doi:10.1124/jpet.104.076653. PMID 15608085. 
  2. ^ "Advisories, Warnings and Recalls - 2001". Health Canada. 7 January 2009. Archived from the original on 3 May 2010. 
  3. ^ "Drugs Banned In India". Dte.GHS, Ministry of Health and Family Welfare, Government of India. Central Drugs Standard Control Organization. Retrieved 7 January 2014. 
  4. ^ "Rinexin in Farmaceutiska Specialiteter i Sverige" ["Rinexin" from the Pharmaceutical Specialties of Sweden] (drug catalog) (in Swedish). Retrieved 7 January 2014. 
  5. ^ "Phenylpopanolamine Advisory" (Press release). US Food and Drug Administration. 6 November 2000. Archived from the original on 26 January 2010. 
  6. ^ "Phenylpropanolamine (PPA) Information Page - FDA moves PPA from OTC" (Press release). US Food and Drug Administration. 23 December 2005. Archived from the original on 12 January 2009. 
  7. ^ "Implementation of the international drug control treaties: changes in the scope of control of substances". Vienna: Commission on Narcotic Drugs, Forty-third session. 6–15 March 2000. Archived from the original on 14 August 2003. 
  8. ^ "Unsafe Drugs- nimesulide, Cisapride, Phenylpropanolamine Banned". 
  9. ^ "Madras High Court Revokes Ban on Manufacture and Sale PPA". Scribd.com. 13 September 2011. Retrieved 7 January 2014. 
  10. ^ Sulzer, D.; Sonders, M.S.; Poulsen, N.W. et al. (April 2005). "Mechanisms of neurotransmitter release by amphetamines: a review" (PDF). Prog. Neurobiol. 75 (6): 406–33. doi:10.1016/j.pneurobio.2005.04.003. PMID 15955613. 

References[edit]

External links[edit]