塩酸フェニルプロパノールアミン

関: phenylpropanolamine、prolamine

WordNet

a simple protein found in plants
an adrenergic drug used in many preparations to relieve allergic reactions or respiratory infections; "drugs containing phenylpropanolamine are being recalled"
a complex consisting of an organic base in association with hydrogen chloride

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/05/20 21:37:57」(JST)

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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 In Canada, it was withdrawn from the market on 31 May 2001.^[2] In India human use of PPA and its formulations were banned on 10 February 2011,^[3] but the ban was overturned by the court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]

Pharmacology

Phenylpropanolamine acts as an alpha-adrenergic receptor and beta-adrenergic receptor agonist as well as a dopamine receptor D1 partial agonist.^[5]

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.

Metabolic pathways of amphetamine

4-Hydroxyphenylacetone

Phenylacetone

Benzoic acid

Hippuric acid

Amphetamine

Norephedrine

4-Hydroxyamphetamine

4-Hydroxynorephedrine

Para-
Hydroxylation

Beta-
Hydroxylation

Oxidative
Deamination

Oxidation

Glycine
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,^[6] 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^[7] 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.^[8] 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.^[9]

Drugs containing PPA were banned in India on 27 January 2011.^[10] On 13 September 2011 Madras High Court revoked a ban on manufacture and sale of paediatric drugs nimesulide and phenylpropanolamine (PPA).^[11]

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").^[12]

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.^[13] The methyl group on the alpha carbon (the first carbon before the nitrogen group) also makes this compound a member of the amphetamine family.^[13] 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.^[13] However, the addition of the α-methyl group allows the compound to avoid metabolism and confer an effect.^[13] In general, N-methylation of primary amines increases their potency; whereas β-hydroxylation decreases CNS activity, but conveys more selectivity for adrenergic receptors.^[13]

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/
^ "Phenylpropanolamine". DrugBank. University of Alberta. Retrieved 10 November 2014.
^ "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.
^ ^a ^b ^c ^d ^e Westfall DP, Westfall TC (2010). "Chapter 12: Adrenergic Agonists and Antagonists: CLASSIFICATION OF SYMPATHOMIMETIC DRUGS". In Brunton LL, Chabner BA, Knollmann BC. Goodman & Gilman's Pharmacological Basis of Therapeutics (12th ed.). New York: McGraw-Hill. ISBN 9780071624428. CHEMISTRY AND STRUCTURE-ACTIVITY RELATIONSHIP OF SYMPATHOMIMETIC AMINES
β-Phenylethylamine (Table 12–1) can be viewed as the parent compound of the sympathomimetic amines, consisting of a benzene ring and an ethylamine side chain. The structure permits substitutions to be made on the aromatic ring, the α- and β-carbon atoms, and the terminal amino group to yield a variety of compounds with sympathomimetic activity. ...N-methylation increases the potency of primary amines ...
Substitution on the α-Carbon Atom
This substitution blocks oxidation by MAO, greatly prolonging the duration of action of non-catecholamines because their degradation depends largely on the action of this enzyme. The duration of action of drugs such as ephedrine or amphetamine is thus measured in hours rather than in minutes. Similarly, compounds with an α-methyl substituent persist in the nerve terminals and are more likely to release NE from storage sites. Agents such as metaraminol exhibit a greater degree of indirect sympathomimetic activity.
Substitution on the β-Carbon Atom
Substitution of a hydroxyl group on the β carbon generally decreases actions within the CNS, largely because it lowers lipid solubility. However, such substitution greatly enhances agonist activity at both α- and β- adrenergic receptors. Although ephedrine is less potent than methamphetamine as a central stimulant, it is more powerful in dilating bronchioles and increasing blood pressure and heart rate.

References

Hartung, W. H.; Munch, J. C. (1929). "Amino Alcohols. I. Phenylpropanolamine and Para-Tolylpropanolamine". Journal of the American Chemical Society 51 (7): 2262. doi:10.1021/ja01382a044. edit
Hartung, W. H.; Chang, Y. T. (1952). "Palladium Catalysis. IV.1Change in the Behavior of Palladium-on-Charcoal in Hydrogenation Reactions2". 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

UpToDate Contents

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1. フェニレフリンおよび類似構造のうっ血除去薬：小児の中毒 phenylephrine and related decongestants pediatric poisoning
2. OTC咳止め・かぜ薬：小児の中毒へのアプローチ over the counter cough and cold preparations approach to pediatric poisoning
3. 小児における感冒：治療および予防 the common cold in children treatment and prevention
4. 脳卒中サブタイプの臨床診断 clinical diagnosis of stroke subtypes
5. 成人における肥満：薬物療法 obesity in adults drug therapy

English Journal

Validation of a population-based method to assess drug-induced alterations in the QT interval: a self-controlled crossover study.

Iribarren C, Round AD, Peng JA, Lu M, Zaroff JG, Holve TJ, Prasad A, Stang P.SourceDivision of Research, Kaiser Permanente Medical Care Program, Oakland, CA, USA.
Pharmacoepidemiology and drug safety.Pharmacoepidemiol Drug Saf.2013 Jul 16. doi: 10.1002/pds.3479. [Epub ahead of print]
PURPOSE: The purpose of this study was to ascertain, in the context of an integrated health care delivery system, the association between a comprehensive list of drugs known to have potential QT liability and QT prolongation or shortening.METHODS: By using a self-controlled crossover study with 59�
PMID 23857878

Use of decongestants during pregnancy and the risk of birth defects.

Yau WP, Mitchell AA, Lin KJ, Werler MM, Hernández-Díaz S.AbstractPrevious studies suggested that early pregnancy exposure to specific oral decongestants increases the risks of several birth defects. Using January 1993-January 2010 data from the Slone Epidemiology Center Birth Defects Study, we tested those hypotheses among 12,734 infants with malformations (cases) and 7,606 nonmalformed control infants in the United States and Canada. Adjusted odds ratios and 95% confidence intervals were estimated for specific birth defects, with controlling for potential confounders. Findings did not replicate several hypotheses but did support 3 previously reported associations: phenylephrine and endocardial cushion defect (odds ratio = 8.0; 95% confidence interval: 2.5, 25.3; 4 exposed cases), phenylpropanolamine and ear defects (odds ratio = 7.8; 95% confidence interval: 2.2, 27.2; 4 exposed cases), and phenylpropanolamine and pyloric stenosis (odds ratio = 3.2; 95% confidence interval: 1.1, 8.8; 6 exposed cases). Hypothesis-generating analyses involving multiple comparisons identified a small number of associations with oral and intranasal decongestants. Accumulating evidence supports associations between first-trimester use of specific oral and possibly intranasal decongestants and the risk of some infrequent specific birth defects.
American journal of epidemiology.Am J Epidemiol.2013 Jul 15;178(2):198-208. doi: 10.1093/aje/kws427. Epub 2013 Jul 3.
Previous studies suggested that early pregnancy exposure to specific oral decongestants increases the risks of several birth defects. Using January 1993-January 2010 data from the Slone Epidemiology Center Birth Defects Study, we tested those hypotheses among 12,734 infants with malformations (cases
PMID 23825167

Improved GC method for the determination of the active principles of Catha edulis.

Dell'acqua L, Roda G, Arnoldi S, Rusconi C, Turati L, Gambaro V.SourceDipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Luigi Mangiagalli 25, 20133 Milano, Italy.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.J Chromatogr B Analyt Technol Biomed Life Sci.2013 Jun 15;929:142-8. doi: 10.1016/j.jchromb.2013.04.012. Epub 2013 Apr 18.
The GC method previously reported by our research group for the analysis of the active principles of Catha edulis, i.e. cathine, cathinone and phenylpropanolamine, was considerably improved. N-methyl-N-trimethylsilyl-trifluoroacetamide (MSTFA) as derivatizing agent was employed, thus allowing an acc
PMID 23685239

Japanese Journal

Voltammetric Analysis of Phenylpropanolamine Hydrochloride at the Water|Nitrobenzene Interface

ポーラログラフィー 57(3), 239, 2011-11-21
NAID 10030204774

Analysis of the Release Process of Phenylpropanolamine Hydrochloride from Ethylcellulose Matrix Granules V. : Release Properties of Ethylcellulose Layered Matrix Granules

Chemical & pharmaceutical bulletin 56(4), 525-529, 2008-04-01
NAID 110006649357

Analysis of the Release Process of Phenylpropanolamine Hydrochloride from Ethylcellulose Matrix Granules IV. Evaluation of the Controlled Release Properties for in Vivo and in Vitro Release Systems

Chemical & pharmaceutical bulletin 55(11), 1569-1573, 2007-11-01
NAID 110006437252

「フェニルプロパノールアミン」

Phenylpropanolamine
Systematic (IUPAC) name
	(1S,2R)-2-amino-1-phenylpropan-1-ol
Clinical data
Trade names	Acutrim
AHFS/Drugs.com	Multum Consumer Information
Legal status	AU: Prescription Only (S4); UK: Unknown; US: List I chemical; Prescription-only;
Routes of; administration	Oral
Pharmacokinetic data
Metabolism	Hepatic: CYP2D6
Half-life	2.1–3.4 hours
Identifiers
CAS Registry Number	14838-15-4
ATC code	R01BA01 QG04BX91
PubChem	CID 10297
DrugBank	DB00397
ChemSpider	9875
UNII	33RU150WUN
KEGG	D08368
ChEMBL	CHEMBL136560
Chemical data
Formula	C9H13NO
Molecular mass	151.206 g/mol
	SMILES O[C@H](c1ccccc1)[C@@H](N)C;
	InChI InChI=1S/C9H13NO/c1-7(10)9(11)8-5-3-2-4-6-8/h2-7,9,11H,10H2,1H3/t7-,9-/m0/s1 ; Key:DLNKOYKMWOXYQA-CBAPKCEASA-N ;
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　　[★]

英: phenylpropanolamine、phenylpropanolamine hydrochloride
関: プロラミン、塩酸フェニルプロパノールアミン

「塩酸フェニルプロパノールアミン」

　　[★]

英: phenylpropanolamine hydrochloride
関: フェニルプロパノールアミン、プロラミン

「prolamine」

　　[★]

プロラミン

関: phenylpropanolamine、phenylpropanolamine hydrochloride

「hydrochloride」

　　[★] 塩酸塩、ハイドロクロライド　

[pmid15608085-1] 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] ttp://www.indiamedicaltimes.com/2011/09/13/madras-high-court-revokes-ban-on-manufacture-and-sale-of-paediatric-drugs-nimesulide-and-ppa/

[5] "Phenylpropanolamine". DrugBank. University of Alberta. Retrieved 10 November 2014.

[6] "Rinexin in Farmaceutiska Specialiteter i Sverige" ["Rinexin" from the Pharmaceutical Specialties of Sweden] (drug catalog) (in Swedish). Retrieved 7 January 2014.

[7] "Phenylpopanolamine Advisory" (Press release). US Food and Drug Administration. 6 November 2000. Archived from the original on 26 January 2010.

[8] "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.

[9] 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.

[10] "Unsafe Drugs- nimesulide, Cisapride, Phenylpropanolamine Banned".

[11] "Madras High Court Revokes Ban on Manufacture and Sale PPA". Scribd.com. 13 September 2011. Retrieved 7 January 2014.

[pmid15955613-12] 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.

[Westfall2-13] Westfall DP, Westfall TC (2010). "Chapter 12: Adrenergic Agonists and Antagonists: CLASSIFICATION OF SYMPATHOMIMETIC DRUGS". In Brunton LL, Chabner BA, Knollmann BC. Goodman & Gilman's Pharmacological Basis of Therapeutics (12th ed.). New York: McGraw-Hill. ISBN 9780071624428. CHEMISTRY AND STRUCTURE-ACTIVITY RELATIONSHIP OF SYMPATHOMIMETIC AMINES
β-Phenylethylamine (Table 12–1) can be viewed as the parent compound of the sympathomimetic amines, consisting of a benzene ring and an ethylamine side chain. The structure permits substitutions to be made on the aromatic ring, the α- and β-carbon atoms, and the terminal amino group to yield a variety of compounds with sympathomimetic activity. ...N-methylation increases the potency of primary amines ...
Substitution on the α-Carbon Atom
This substitution blocks oxidation by MAO, greatly prolonging the duration of action of non-catecholamines because their degradation depends largely on the action of this enzyme. The duration of action of drugs such as ephedrine or amphetamine is thus measured in hours rather than in minutes. Similarly, compounds with an α-methyl substituent persist in the nerve terminals and are more likely to release NE from storage sites. Agents such as metaraminol exhibit a greater degree of indirect sympathomimetic activity.
Substitution on the β-Carbon Atom
Substitution of a hydroxyl group on the β carbon generally decreases actions within the CNS, largely because it lowers lipid solubility. However, such substitution greatly enhances agonist activity at both α- and β- adrenergic receptors. Although ephedrine is less potent than methamphetamine as a central stimulant, it is more powerful in dilating bronchioles and increasing blood pressure and heart rate.

リンク元	「フェニルプロパノールアミン」「塩酸フェニルプロパノールアミン」「prolamine」
関連記事	「hydrochloride」

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phenylpropanolamine hydrochloride