Identification

Name
Phenylpropanolamine
Accession Number
DB00397  (APRD00457, DB09441)
Type
Small Molecule
Groups
Approved, Vet approved, Withdrawn
Description

Phenylpropanolamine has been withdrawn in Canada and the United States. In November 2000, the Food and Drug Administration (FDA) issued a public health advisory against the use of the drug.

Structure
Thumb
Synonyms
  • (+-)-Norephedrine
  • (+-)-Phenylpropanolamine
  • Fenilpropanolamina
  • Norephedrine
  • Phenylpropanolamin
  • Phenylpropanolamina
  • Phenylpropanolamine
  • Phénylpropanolamine
  • Phenylpropanolaminum
  • PPA
Product Ingredients
IngredientUNIICASInChI Key
Phenylpropanolamine hydrochlorideB4HG4K9HF5154-41-6DYWNLSQWJMTVGJ-KUSKTZOESA-N
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Antitussive Decong Antihistamine SyrPhenylpropanolamine hydrochloride (13 mg) + Dextromethorphan hydrobromide (15 mg) + Mepyramine maleate (6.5 mg) + Pheniramine maleate (6.5 mg)SyrupOralProdemdis Enr.1992-12-312001-04-26Canada
Bronchodex D CapPhenylpropanolamine hydrochloride (50 mg) + Chlorpheniramine maleate (1 mg) + Pheniramine maleate (12.5 mg)Capsule, extended releaseOralProdemdis Enr.1981-12-312001-04-26Canada
Bronchosirum Pour EnfantsPhenylpropanolamine hydrochloride (12.5 mg) + Dextromethorphan hydrobromide (15 mg) + Mepyramine maleate (6.25 mg) + Pheniramine maleate (6.25 mg)SyrupOralBronchosirum Inc.1987-12-311997-08-05Canada
Caldomine Dh AdultePhenylpropanolamine hydrochloride (25 mg) + Hydrocodone bitartrate (5 mg) + Mepyramine maleate (12.5 mg) + Pheniramine maleate (12.5 mg)LiquidOralTechnilab Pharma Inc.1981-12-312001-04-04Canada
Caldomine Dh EnfantPhenylpropanolamine hydrochloride (12.5 mg) + Hydrocodone bitartrate (1.667 mg) + Mepyramine maleate (6.25 mg) + Pheniramine maleate (6.25 mg)LiquidOralTechnilab Pharma Inc.1982-12-312001-04-04Canada
Centracol DM - SyrPhenylpropanolamine hydrochloride (12.5 mg) + Dextromethorphan hydrobromide (15 mg) + Mepyramine maleate (6.25 mg) + Pheniramine maleate (6.25 mg)SyrupOralPrometic Pharma Inc.1994-12-311999-08-12Canada
Chlor Tripolon Decongest SyrPhenylpropanolamine hydrochloride (2.5 mg) + Chlorpheniramine maleate (.4 mg)SyrupOralSchering Plough1981-12-312000-07-11Canada
Cold & Allergy Relief - LiqPhenylpropanolamine hydrochloride (5 mg) + Brompheniramine maleate (4 mg) + Phenylephrine hydrochloride (5 mg)LiquidOralStanley Pharmaceuticals, A Division Of Vita Health Products Inc.1996-12-312001-04-09Canada
Cold Decongestant Long Acting CapPhenylpropanolamine hydrochloride (50 mg) + Chlorpheniramine maleate (1 mg) + Pheniramine maleate (12.5 mg)Capsule, extended releaseOralNovopharm Limited1969-12-312001-04-12Canada
Cold ReliefPhenylpropanolamine hydrochloride (12.5 mg) + Brompheniramine maleate (2 mg)LiquidOralPerrigo International1997-11-302001-03-07Canada
International/Other Brands
Acutrim / Boxogetten (Cheplapharm) / Dexatrim / Disudrin (Pediatrica) / Naldec (IAE) / Nasadec (Medlink) / Nasathera (Morishita-Seggs) / Propagest / Recatol mono (Riemser) / Rhindecon / Rinexin (Meda)
Categories
UNII
57B9YG5Y1E
CAS number
14838-15-4
Weight
Average: 151.209
Monoisotopic: 151.099714043
Chemical Formula
C9H13NO
InChI Key
DLNKOYKMWOXYQA-CBAPKCEASA-N
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
IUPAC Name
(1R,2S)-2-amino-1-phenylpropan-1-ol
SMILES
[H][C@@](C)(N)[C@]([H])(O)C1=CC=CC=C1

Pharmacology

Indication

For the treatment of nasal congestion, control of urinary incontinence, priapism and obesity.

Pharmacodynamics

Phenylpropanolamine (PPA), a sympathomimetic agent structurally similar to pseudoephedrine, is used to treat nasal congestion. Phenylpropanolamine is found in appetite suppressant formulations and with guaifenesinin in cough-cold formulations. In 2000, the FDA requested that all drug companies discontinue marketing products containing phenylpropanolamine, due to an increased risk of hemorrhagic stroke in women who used phenylpropanolamine.

Mechanism of action

Phenylpropanolamine acts directly on alpha- and, to a lesser degree, beta-adrenergic receptors in the mucosa of the respiratory tract. Stimulation of alpha-adrenergic receptors produces vasoconstriction, reduces tissue hyperemia, edema, and nasal congestion, and increases nasal airway patency. PPA indirectly stimulates beta-receptors, producing tachycardia and a positive inotropic effect.

TargetActionsOrganism
UD(1A) dopamine receptor
partial agonist
Human
UBeta-1 adrenergic receptor
agonist
Human
UBeta-2 adrenergic receptor
agonist
Human
UAlpha-2 adrenergic receptorsNot AvailableHuman
Absorption

Reduced bioavailability (about 38%) from gastrointestinal tract because of first pass metabolism by monoamine oxidase in the stomach and liver.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic

Route of elimination
Not Available
Half life

2.1 to 3.4 hours.

Clearance
Not Available
Toxicity

May induce ventricular extrasystoles and short paroxysms of ventricular tachycardia, a sensation of fullness in the head and tingling of the extremities; LD50=1490mg/kg (orally in rat)

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic AcidThe risk or severity of hypertension can be increased when Phenylpropanolamine is combined with 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
1-benzylimidazoleThe risk or severity of hypertension can be increased when Phenylpropanolamine is combined with 1-benzylimidazole.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of adverse effects can be increased when Phenylpropanolamine is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Phenylpropanolamine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe risk or severity of adverse effects can be increased when Phenylpropanolamine is combined with 3-isobutyl-1-methyl-7H-xanthine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when Phenylpropanolamine is combined with 3,4-Methylenedioxyamphetamine.
3,5-diiodothyropropionic acidThe therapeutic efficacy of Phenylpropanolamine can be increased when used in combination with 3,5-diiodothyropropionic acid.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Phenylpropanolamine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineThe risk or severity of hypertension can be increased when Phenylpropanolamine is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of hypertension can be increased when Phenylpropanolamine is combined with 5-methoxy-N,N-dimethyltryptamine.
Food Interactions
  • Limit caffeine intake.
  • Take without regard to meals.

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0001942
KEGG Compound
C16719
PubChem Compound
26934
PubChem Substance
46508087
ChemSpider
9875
BindingDB
50405613
ChEBI
80680
ChEMBL
CHEMBL136560
Therapeutic Targets Database
DNC001144
PharmGKB
PA164748965
Drugs.com
Drugs.com Drug Page
Wikipedia
Phenylpropanolamine
ATC Codes
R01BA51 — Phenylpropanolamine, combinationsR01BA01 — Phenylpropanolamine
MSDS
Download (52.4 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Amerisource Health Services Corp.
  • Boca Pharmacal
  • Breckenridge Pharmaceuticals
  • Bristol-Myers Squibb Co.
  • C.O. Truxton Inc.
  • Carlisle Laboratories Inc.
  • Century Pharmaceuticals Inc.
  • Chattem Chemicals Inc.
  • Corvit Pharmaceuticals
  • DHHS Program Support Center Supply Service Center
  • Direct Dispensing Inc.
  • Duramed
  • Econolab Inc.
  • Equipharm Inc.
  • Farmaquimia SA de CV
  • Generics Puerto Rico Inc.
  • Gm Pharmaceuticals Inc.
  • Golden State Medical Supply Inc.
  • H and H Laboratories
  • Hi Tech Pharmacal Co. Inc.
  • International Ethical Labs Inc.
  • Iopharm Laboratories Inc.
  • Kaiser Foundation Hospital
  • Kraft Pharmaceutical Co. Inc.
  • Lark Pharmaceuticals Inc.
  • Llorens Pharmaceutical
  • Long Island Pharmacal
  • Major Pharmaceuticals
  • Mallinckrodt Inc.
  • Mcgregor Pharmaceuticals Inc.
  • Midland Pharmaceutical LLC
  • Murfreesboro Pharmaceutical Nursing Supply
  • Nexgen Pharma Inc.
  • Norega Laboratories Inc.
  • Novartis AG
  • Pamlab LLC
  • Patient First Corp.
  • PD-Rx Pharmaceuticals Inc.
  • Pecos Pharmaceutical Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Prometic Pharma Inc.
  • Qualitest
  • Respa Pharmaceuticals Inc.
  • Sandhills Packaging Inc.
  • Sanofi-Aventis Inc.
  • Seatrace Pharmaceuticals Inc.
  • Southwood Pharmaceuticals
  • St Mary's Medical Park Pharmacy
  • Talbert Medical Management Corp.
  • Topco
  • Tri Med Laboratories Inc.
  • United Research Laboratories Inc.
  • Veratex Corp.
  • Vista Pharmaceuticals Inc.
Dosage forms
FormRouteStrength
SuspensionOral
SyrupOral
ElixirOral
Tablet, extended releaseOral
CapsuleOral
Solution / dropsOral
TabletOral
LiquidOral
Capsule, extended releaseOral
Prices
Unit descriptionCostUnit
Naldecon Senior EX 200 mg/5ml Syrup 118ml Bottle15.99USD bottle
Entex ER 10-300 mg 12 Hour Capsule1.14USD capsule
Codimal la capsule0.7USD capsule
Despec-dm tablet0.61USD tablet
Despec-tab tablet0.47USD tablet
Triaminic allergy thin strip0.35USD strip
Triaminic cold-stuff nose strip0.35USD strip
Conex tablet0.33USD tablet
Triaminic cgh-runny nose strip0.3USD strip
Triaminic cough strips0.3USD strip
Triaminic cough-cold chew0.27USD each
Triaminic softchew tablet0.27USD tablet
Triaminic softchews tablet0.25USD tablet
Childrens triaminic decon spray0.24USD ml
Triaminicin tablet0.23USD tablet
Dexatrim natural caplet0.19USD caplet
Codimal DH 5-8.33-1.66 mg/5ml Syrup0.18USD ml
Despec-exp syrup0.18USD ml
Codimal dm syrup0.16USD ml
Naldecon-dx senior0.06USD ml
Apap allergy sinus caplet0.05USD caplet
Triaminic chest-nasal cong liq0.04USD ml
Triaminic cold & cough liquid0.04USD ml
Triaminic cold-allergy pe liq0.04USD ml
Triaminic cough-nasal cong liquid0.04USD ml
Triaminic cough-sore throat liquid0.04USD ml
Triaminic flu cough-fever suspension0.04USD ml
Triaminic flu-cough-fever liquid0.04USD ml
Triaminic-d syrup0.04USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)190-194 °CNot Available
water solubilityFreely solubleNot Available
logP0.67SANGSTER (1994)
pKa9.44 (at 20 °C)PERRIN,DD (1965)
Predicted Properties
PropertyValueSource
Water Solubility20.6 mg/mLALOGPS
logP0.57ALOGPS
logP0.89ChemAxon
logS-0.87ALOGPS
pKa (Strongest Acidic)13.9ChemAxon
pKa (Strongest Basic)9.37ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area46.25 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity44.91 m3·mol-1ChemAxon
Polarizability16.89 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9871
Blood Brain Barrier+0.5843
Caco-2 permeable+0.7568
P-glycoprotein substrateNon-substrate0.7276
P-glycoprotein inhibitor INon-inhibitor0.9849
P-glycoprotein inhibitor IINon-inhibitor0.9917
Renal organic cation transporterNon-inhibitor0.9113
CYP450 2C9 substrateNon-substrate0.8077
CYP450 2D6 substrateNon-substrate0.8418
CYP450 3A4 substrateNon-substrate0.8063
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.9261
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9096
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.6929
BiodegradationNot ready biodegradable0.6917
Rat acute toxicity2.0244 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9446
hERG inhibition (predictor II)Non-inhibitor0.937
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Partial agonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name
DRD1
Uniprot ID
P21728
Uniprot Name
D(1A) dopamine receptor
Molecular Weight
49292.765 Da
References
  1. Cheng JT, Kuo DY: Both alpha1-adrenergic and D(1)-dopaminergic neurotransmissions are involved in phenylpropanolamine-mediated feeding suppression in mice. Neurosci Lett. 2003 Aug 21;347(2):136-8. [PubMed:12873745]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Receptor signaling protein activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately e...
Gene Name
ADRB1
Uniprot ID
P08588
Uniprot Name
Beta-1 adrenergic receptor
Molecular Weight
51322.1 Da
References
  1. Thomas SH, Clark KL, Allen R, Smith SE: A comparison of the cardiovascular effects of phenylpropanolamine and phenylephrine containing proprietary cold remedies. Br J Clin Pharmacol. 1991 Dec;32(6):705-11. [PubMed:1722692]
  2. Moya-Huff FA, Maher TJ: Adrenergic receptor subtype activation by (+)-, (-)- and (+/-)-norephedrine in the pithed rat. J Pharm Pharmacol. 1987 Feb;39(2):108-12. [PubMed:2881994]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Protein homodimerization activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately ...
Gene Name
ADRB2
Uniprot ID
P07550
Uniprot Name
Beta-2 adrenergic receptor
Molecular Weight
46458.32 Da
References
  1. Moya-Huff FA, Maher TJ: Adrenergic receptor subtype activation by (+)-, (-)- and (+/-)-norephedrine in the pithed rat. J Pharm Pharmacol. 1987 Feb;39(2):108-12. [PubMed:2881994]
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
General Function
Thioesterase binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...

Components:
References
  1. Flavahan NA: Phenylpropanolamine constricts mouse and human blood vessels by preferentially activating alpha2-adrenoceptors. J Pharmacol Exp Ther. 2005 Apr;313(1):432-9. Epub 2004 Dec 17. [PubMed:15608085]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serotonin binding
Specific Function
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
Gene Name
MAOA
Uniprot ID
P21397
Uniprot Name
Amine oxidase [flavin-containing] A
Molecular Weight
59681.27 Da
References
  1. Yu PH: Inhibition of monoamine oxidase activity by phenylpropanolamine, an anorectic agent. Res Commun Chem Pathol Pharmacol. 1986 Feb;51(2):163-71. [PubMed:3961266]

Drug created on June 13, 2005 07:24 / Updated on December 16, 2018 07:03