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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/09/19 11:18:16」(JST)
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| Systematic (IUPAC) name | |
|---|---|
| 2-amino-1-phenylpropan-1-ol | |
| Clinical data | |
| Trade names | Acutrim |
| AHFS/Drugs.com | Multum Consumer Information |
| Legal status |
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| Routes | Oral |
| Pharmacokinetic data | |
| Half-life | 2.1 — 3.4 hours |
| Identifiers | |
| CAS number | 14838-15-4 Y |
| ATC code | R01BA01 QG04BX91 |
| PubChem | CID 10297 |
| DrugBank | DB00397 |
| ChemSpider | 9875 Y |
| UNII | 33RU150WUN Y |
| KEGG | D08368 Y |
| ChEMBL | CHEMBL136560 Y |
| Chemical data | |
| Formula | C9H13NO |
| Mol. mass | 151.206 g/mol |
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| Y (what is this?) (verify) | |
Phenylpropanolamine (BAN and INN; PPA, β-hydroxyamphetamine), 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 In Canada, it was withdrawn from the market on 31 May 2001.[2] In India human use of PPA and its formulations were banned on 10 February 2011.[3] but the ban was overturned by the court in September 2011.[4]
Contents
- 1 Pharmacology
- 2 Legal status
- 3 Chemistry
- 4 Synthesis
- 5 See also
- 6 Notes
- 7 References
- 8 External links
Pharmacology
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.
Metabolic pathways of amphetamine
4-Hydroxyphenylacetone
Phenylacetone
Benzoic acid
Hippuric acid
Amphetamine
Norephedrine
4-Hydroxyamphetamine
4-Hydroxynorephedrine
Para-
Hydroxylation
Hydroxylation
Para-
Hydroxylation
Hydroxylation
Para-
Hydroxylation
Hydroxylation
Beta-
Hydroxylation
Hydroxylation
Beta-
Hydroxylation
Hydroxylation
Oxidative
Deamination
Deamination
Oxidation
Glycine
Conjugation
Conjugation
In humans, norephedrine occurs as a metabolite of amphetamine. The beta-hydroxylation of amphetamine is mediated by dopamine β-hydroxylase.
Legal status
In Europe, PPA is still available in prescription decongestants such as Rinexin,[5] 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[when?], 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[6] 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.[7] 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.[8]
Drugs containing PPA were banned in India on 27 January 2011.[9] On 13 September 2011 Madras High Court revoked a ban on manufacture and sale of paediatric drugs nimesulide and phenylpropanolamine (PPA).[10]
Chemistry
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").[11]
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.
Synthesis
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:[12][13][14] U.S. Patent 3,028,429
Alternatively, it might be expected to react benzaldehyde with nitroethane (c.f. Henry reaction), then reduce this without dehydration step.
See also
- Amphetamine
- Ephedrine
- Methamphetamine
- Pseudoephedrine
- Substituted amphetamine
Notes
- ^ 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.
- ^ "Advisories, Warnings and Recalls - 2001". Health Canada. 7 January 2009. Archived from the original on 3 May 2010.
- ^ "Drugs Banned In India". Dte.GHS, Ministry of Health and Family Welfare, Government of India. Central Drugs Standard Control Organization. Retrieved 7 January 2014.
- ^ http://www.indiamedicaltimes.com/2011/09/13/madras-high-court-revokes-ban-on-manufacture-and-sale-of-paediatric-drugs-nimesulide-and-ppa/
- ^ "Rinexin in Farmaceutiska Specialiteter i Sverige" ["Rinexin" from the Pharmaceutical Specialties of Sweden] (drug catalog) (in Swedish). Retrieved 7 January 2014.
- ^ "Phenylpopanolamine Advisory" (Press release). US Food and Drug Administration. 6 November 2000. Archived from the original on 26 January 2010.
- ^ "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.
- ^ "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.
- ^ "Unsafe Drugs- nimesulide, Cisapride, Phenylpropanolamine Banned".
- ^ "Madras High Court Revokes Ban on Manufacture and Sale PPA". Scribd.com. 13 September 2011. Retrieved 7 January 2014.
- ^ 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.
- ^ Nagai†, W. N.; Kanao, S. Z. (1929). "Über die Synthese der isomeren Ephedrine und ihrer Homologen". Justus Liebig's Annalen der Chemie 470: 157. doi:10.1002/jlac.19294700110. edit
- ^ Hartung, W. H.; Munch, J. C. (1929). Journal of the American Chemical Society 51 (7): 2262. doi:10.1021/ja01382a044. edit
- ^ Hartung, W. H.; Chang, Y. T. (1952). Journal of the American Chemical Society 74 (23): 5927. doi:10.1021/ja01143a031. edit
References
- Hartung, W. H.; Munch, J. C. (1929). Journal of the American Chemical Society 51 (7): 2262. doi:10.1021/ja01382a044. edit
- Hartung, W. H.; Chang, Y. T. (1952). Journal of the American Chemical Society 74 (23): 5927. doi:10.1021/ja01143a031. edit
- W. N. Nagai, S. Kanao, Ann. Chem., 470, 157 (1929).
- G. Wilbert, P. Sosis, U.S. Patent 3,028,429 (1962).
External links
- Phenylpropanolamine Information Page at FDA.gov (update, includes earlier reports)
- U.S. National Library of Medicine: Drug Information Portal - Phenylpropanolamine
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English Journal
- Vasorelaxant effects of 2-nitro-1-phenyl-1-propanol in rat aorta.
- de Brito TS1, de Lima FJ1, Gadelha KK1, da Fonseca Magalhães PA1, Lahlou S1, Magalhães PJ1.
- Clinical and experimental pharmacology & physiology.Clin Exp Pharmacol Physiol.2016 Jul 20. doi: 10.1111/1440-1681.12625. [Epub ahead of print]
- 2-Nitro-1-phenyl-1-propanol (NPP) is a nitro alcohol that is known as an intermediate in the synthesis of sympathomimetic agents, such as norephedrine. The present study investigated the vasoactive effects of NPP on rat aorta. In endothelium-intact aortic rings, NPP fully relaxed contractions that w
- PMID 27437904
- The Methylene Alkoxy Carbamate Self-Immolative Unit: Utilization for the Targeted Delivery of Alcohol-Containing Payloads with Antibody-Drug Conjugates.
- Kolakowski RV1, Haelsig KT2, Emmerton KK2, Leiske CI2, Miyamoto JB2, Cochran JH2, Lyon RP2, Senter PD2, Jeffrey SC3.
- Angewandte Chemie (International ed. in English).Angew Chem Int Ed Engl.2016 Jul 4;55(28):7948-51. doi: 10.1002/anie.201601506. Epub 2016 May 20.
- A strategy for the conjugation of alcohol-containing payloads to antibodies has been developed and involves the methylene alkoxy carbamate (MAC) self-immolative unit. A series of MAC β-glucuronide model constructs were prepared to evaluate stability and enzymatic release, and the results demonstrat
- PMID 27198854
- A (-)-norephedrine-based molecularly imprinted polymer for the solid-phase extraction of psychoactive phenylpropylamino alkaloids from Khat (Catha edulis Vahl. Endl.) chewing leaves.
- Atlabachew M1,2, Torto N3, Chandravanshi BS4, Redi-Abshiro M4, Chigome S3, Mothibedi K3, Combrinck S1.
- Biomedical chromatography : BMC.Biomed Chromatogr.2016 Jul;30(7):1007-15. doi: 10.1002/bmc.3643. Epub 2015 Dec 1.
- A molecularly imprinted polymer (MIP) was prepared using (-)-norephedrine as the template, methacrylic acid as the functional monomer, ethylene glycol dimethacrylate as the cross-linker and chloroform as the porogen. The MIP was used as a selective sorbent in the molecularly imprinted solid-phase ex
- PMID 26531856
Japanese Journal
- Convenient method for synthesis of l-methamphetamine
- 間 忍,市川 聡,米林 史博
- 日本法科学技術学会誌 13(1), 67-72, 2008-02
- NAID 40015989559
- Convenient Method for Synthesis of l-Methamphetamine
- , ,
- 日本法科学技術学会誌 13(1), 67-72, 2008
- … We developed a new and convenient method for the synthesis of l-MA using d-norephedrine (d-NE) as a starting material. …
- NAID 130004942618
- Stability studies of amphetamine and ephedrine derivatives in urine
- JIMENEZ C.,DE LA TORRE R.,VENTURA M.,SEGURA J.,VENTURA R.
- Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 843(1), 84-93, 2006-10-20
- NAID 10025788150
Related Links
- [(1S,2R)-(+)-Norephedrine] [37577-28-9] | 価格や在庫、物性値などの詳細情報ページです。 ... ・川口の在庫は即日，つくばの在庫は2〜3日以内の出荷となります。・詳細につきましては，お手数ですが営業部までお問い合わせください。
- Structure, properties, spectra, suppliers and links for: (-)-norephedrine, 492-41-1. ... Predicted data is generated using the US Environmental Protection Agency’s EPISuite , for more information see their website. Log Octanol-Water ...
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★リンクテーブル★
| リンク元 | 「ノルエフェドリン」 |
| 拡張検索 | 「p-hydroxynorephedrine」 |