PHENYLPROPANOLAMINE BITARTRATE

US Previously Marketed

First approved in 1941

Details

Stereochemistry	MIXED
Molecular Formula	C9H13NO.C4H6O6
Molecular Weight	301.2925
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0
Stereo Comments	Phenylpropanolamine is racemic and Tartaric acid chiral

SHOW SMILES / InChI

Structure of PHENYLPROPANOLAMINE BITARTRATE

Structure Search

SMILES

O[C@H]([C@@H](O)C(O)=O)C(O)=O.C[C@H](N)[C@H](O)C1=CC=CC=C1

InChI

InChIKey=NCHHVLCKEUNWNJ-IOJVUJSNSA-N

InChI=1S/C9H13NO.C4H6O6/c1-7(10)9(11)8-5-3-2-4-6-8;5-1(3(7)8)2(6)4(9)10/h2-7,9,11H,10H2,1H3;1-2,5-6H,(H,7,8)(H,9,10)/t7-,9-;1-,2-/m01/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8381276 | https://www.google.com/patents/US5260073http://www.sciencedirect.com/science/article/pii/S0099542808601719?via%3Dihub
Curator's Comment: Description was created based on several sources, including http://www.druginfosys.com/drug.aspx?drugcode=569&type=1 | https://www.drugs.com/dosage/phenylpropanolamine.html | https://www.petcarerx.com/medication-guides/about-the-proin-dosage-for-urinary-incontinence/1086?page=all | https://www.federalregister.gov/documents/2014/02/20/2014-03596/phenylpropanolamine-withdrawal-of-approval-of-13-new-drug-applications-and-7-abbreviated-new-drug

Phenylpropanolamine belongs to the sympathomimetic amine class of drugs and is structurally related to ephedrine. The effects of phenylpropanolamine are largely the result of alpha-adrenergic agonist activity resulting from both direct stimulation of adrenergic receptors and release of neuronal norepinephrine. Phenylpropanolamine is mainly used as a nasal decongestant. Phenylpropanolamine is also used as anorexiant in obesity and to treat urinary incontinence in veteranary. Phenylpropanolamine containing products has been withdrawn by FDA due to the association of phenylpropanolamine use with increased risk of hemorrhagic stroke.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Adrenergic receptor alpha-1 169 Target ID: CHEMBL2094251 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8381276	Agonist 2678
Adrenergic receptor alpha 64 Target ID: CHEMBL2095203 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12954796 \| https://www.ncbi.nlm.nih.gov/pubmed/15608085	Agonist 2678
Alpha-1a adrenergic receptor 66 Target ID: CHEMBL319 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12238918	Agonist 2678	9.8 µM [Ki]
Alpha-1b adrenergic receptor 44 Target ID: CHEMBL315 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12238918	Agonist 2678	280.0 µM [EC50]
Alpha-1d adrenergic receptor 36 Target ID: CHEMBL326 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12238918	Agonist 2678	8.4 µM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Sinusitis 26 Sources: https://www.google.com/patents/US5260073	Primary	Not Provided 504	Unknown Approved Use Unknown
Otitis 40 Sources: https://www.google.com/patents/US5260073	Primary	Not Provided 504	Unknown Approved Use Unknown
Nasal congestion 26 Sources: https://www.drugs.com/dosage/phenylpropanolamine.html http://www.druginfosys.com/drug.aspx?drugcode=569&type=1	Primary	Withdrawn	PHENYLPROPANOLAMINE Approved Use Phenylpropanolamine (HCl) is mainly used as a nasal decongestant. Phenylpropanolamine (HCl) is also used as anorexiant in obesity
Obesity 203 Sources: https://www.drugs.com/dosage/phenylpropanolamine.html http://www.druginfosys.com/drug.aspx?drugcode=569&type=1	Primary	Withdrawn	PHENYLPROPANOLAMINE Approved Use Phenylpropanolamine (HCl) is mainly used as a nasal decongestant. Phenylpropanolamine (HCl) is also used as anorexiant in obesity
Nasal congestion 26 Sources: https://www.drugs.com/comments/phenylpropanolamine/	Primary	Withdrawn	CODAMINE Approved Use Unknown Launch Date 2000

C_max

Value	Dose	Co-administered	Analyte	Population
107 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11361053/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		PHENYLPROPANOLAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1104 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11361053/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		PHENYLPROPANOLAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11361053/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		PHENYLPROPANOLAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
225 mg single, oral Overdose Dose: 225 mg Route: oral Route: single Dose: 225 mg Co-administed with:: brompheniramine, p.o(36 mg, single) Sources: https://pubmed.ncbi.nlm.nih.gov/7901355 Page: p.825	healthy, 14 n = 1 Health Status: healthy Age Group: 14 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/7901355 Page: p.825	Disc. AE: Cardiomyopathy... AEs leading to discontinuation/dose reduction: Cardiomyopathy Sources: https://pubmed.ncbi.nlm.nih.gov/7901355 Page: p.825
25 mg 2 times / day multiple, oral Recommended Dose: 25 mg, 2 times / day Route: oral Route: multiple Dose: 25 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12734532 Page: p.100	healthy, 25 n = 1 Health Status: healthy Condition: Weight control Age Group: 25 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/12734532 Page: p.100	Disc. AE: Myocardial infarction... AEs leading to discontinuation/dose reduction: Myocardial infarction Sources: https://pubmed.ncbi.nlm.nih.gov/12734532 Page: p.100
2000 mg single, oral Overdose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Co-administed with:: caffeine, p.o(8 g, single) Sources: https://pubmed.ncbi.nlm.nih.gov/7055513 Page: p.52	unhealthy, 31 n = 1 Health Status: unhealthy Condition: Schizophrenia Age Group: 31 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/7055513 Page: p.52	Disc. AE: Vomiting, Hypertension... AEs leading to discontinuation/dose reduction: Vomiting Hypertension Sources: https://pubmed.ncbi.nlm.nih.gov/7055513 Page: p.52
150 mg single, oral Recommended Dose: 150 mg Route: oral Route: single Dose: 150 mg Co-administed with:: caffeine, p.o(280 mg, single) Sources: https://pubmed.ncbi.nlm.nih.gov/4002267 Page: p.510	healthy, 56 n = 1 Health Status: healthy Condition: Weight control Age Group: 56 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/4002267 Page: p.510	Disc. AE: Headache, Vomiting... AEs leading to discontinuation/dose reduction: Headache (severe) Vomiting Intracranial hemorrhage Sources: https://pubmed.ncbi.nlm.nih.gov/4002267 Page: p.510

AEs

AE	Significance	Dose	Population
Cardiomyopathy	Disc. AE	225 mg single, oral Overdose Dose: 225 mg Route: oral Route: single Dose: 225 mg Co-administed with:: brompheniramine, p.o(36 mg, single) Sources: https://pubmed.ncbi.nlm.nih.gov/7901355 Page: p.825	healthy, 14 n = 1 Health Status: healthy Age Group: 14 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/7901355 Page: p.825
Myocardial infarction	Disc. AE	25 mg 2 times / day multiple, oral Recommended Dose: 25 mg, 2 times / day Route: oral Route: multiple Dose: 25 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12734532 Page: p.100	healthy, 25 n = 1 Health Status: healthy Condition: Weight control Age Group: 25 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/12734532 Page: p.100
Hypertension	Disc. AE	2000 mg single, oral Overdose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Co-administed with:: caffeine, p.o(8 g, single) Sources: https://pubmed.ncbi.nlm.nih.gov/7055513 Page: p.52	unhealthy, 31 n = 1 Health Status: unhealthy Condition: Schizophrenia Age Group: 31 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/7055513 Page: p.52
Vomiting	Disc. AE	2000 mg single, oral Overdose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Co-administed with:: caffeine, p.o(8 g, single) Sources: https://pubmed.ncbi.nlm.nih.gov/7055513 Page: p.52	unhealthy, 31 n = 1 Health Status: unhealthy Condition: Schizophrenia Age Group: 31 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/7055513 Page: p.52
Intracranial hemorrhage	Disc. AE	150 mg single, oral Recommended Dose: 150 mg Route: oral Route: single Dose: 150 mg Co-administed with:: caffeine, p.o(280 mg, single) Sources: https://pubmed.ncbi.nlm.nih.gov/4002267 Page: p.510	healthy, 56 n = 1 Health Status: healthy Condition: Weight control Age Group: 56 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/4002267 Page: p.510
Vomiting	Disc. AE	150 mg single, oral Recommended Dose: 150 mg Route: oral Route: single Dose: 150 mg Co-administed with:: caffeine, p.o(280 mg, single) Sources: https://pubmed.ncbi.nlm.nih.gov/4002267 Page: p.510	healthy, 56 n = 1 Health Status: healthy Condition: Weight control Age Group: 56 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/4002267 Page: p.510
Headache	severe Disc. AE	150 mg single, oral Recommended Dose: 150 mg Route: oral Route: single Dose: 150 mg Co-administed with:: caffeine, p.o(280 mg, single) Sources: https://pubmed.ncbi.nlm.nih.gov/4002267 Page: p.510	healthy, 56 n = 1 Health Status: healthy Condition: Weight control Age Group: 56 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/4002267 Page: p.510

Sourcing

Vendor/Aggregator	ID	URL
ChemIDplus	67244900	https://chem.nlm.nih.gov/chemidplus/id/0067244900
PubChem	118984428	https://pubchem.ncbi.nlm.nih.gov/compound/118984428
Wikidata	Q27274344

PubMed

Title	Date	PubMed
Alpha and beta adrenergic receptor involvement in catecholamine-induced growth of gram-negative bacteria.	1993 Jan 29	8381276
Phenylpropanolamine-induced psychosis. Potential predisposing factors.	1994 Sep	7995508
Dystonic reaction following recommended use of a cold syrup.	1995 Dec	7492048
Clarification--Drug risk in patients with glaucoma.	2001 Jun 11	11417565
Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder.	2001 Mar	11248608
A TLC visualisation reagent for dimethylamphetamine and other abused tertiary amines.	2001 Oct-Dec	11793881
Intense and recurrent déjà vu experiences related to amantadine and phenylpropanolamine in a healthy male.	2001 Sep	11535020
Implementation of the Comprehensive Methamphetamine Control Act of 1996; regulation of pseudoephedrine, phenylpropanolamine, and combination ephedrine drug products and reports of certain transactions to nonregulated persons. Final rule.	2002 Mar 28	11922057
Treatment of overactive bladder: the Antimuscarinic Clinical Effectiveness Trial.	2002 Oct	12354340
A randomized controlled trial of tolterodine and oxybutynin on tolerability and clinical efficacy for treating Chinese women with an overactive bladder.	2002 Sep	12175392
Adrenergic drugs for urinary incontinence in adults.	2003	12804414
Use of Ephedra-containing products and risk for hemorrhagic stroke.	2003 Jan 14	12525737
Intracellular signaling pathways for norepinephrine- and endothelin-1-mediated regulation of myocardial cell apoptosis.	2004 Apr	15124920
Cerebral infarcts in a pediatric patient secondary to phenylpropanolamine, a recalled medication.	2004 Apr	15028328
Fatal pulmonary arterial hypertension associated with phenylpropanolamine exposure.	2004 Jul	15201268
Antimuscarinic agents exhibit local inhibitory effects on muscarinic receptors in bladder-afferent pathways.	2005 Feb	15708029
Should we switch over to tolterodine in every child with non-neurogenic daytime urinary incontinence in whom oxybutynin failed?	2005 Feb	15708055
Medical costs after initiation of drug treatment for overactive bladder: effects of selection bias on cost estimates.	2005 Jul	16161386
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
[Stroke and phenylpropanolamine: what risk factors and what recommendations in request?].	2007	19102094
Treatment of men with lower urinary tract symptoms and overactive bladder.	2007 Mar 21	17374810
Efficacy and safety of combined therapy with terazosin and tolteradine for patients with lower urinary tract symptoms associated with benign prostatic hyperplasia: a prospective study.	2007 Mar 5	17376305
Effect of tolterodine on sleep structure modulated by CYP2D6 genotype.	2008 Jul	17921051
Development and evaluation of oral controlled release chlorpheniramine-ion exchange resinate suspension.	2008 Jul-Aug	20046790
Comparison of fesoterodine and tolterodine in patients with overactive bladder.	2008 Nov	18647298
Asymmetric conjugate reductions of coumarins. A new route to tolterodine and related coumarin derivatives.	2009 Dec 3	19877705
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.	2010 Dec	21818443
Transobturator vaginal tape inside out for treatment of urethral sphincter mechanism incompetence: preliminary results in 7 female dogs.	2010 Dec	20880143

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Nasal Congestion 25 mg (Phenylpropanolamine) orally every 4 hours

Route of Administration: Nasal

In Vitro Use Guide

Unknown

Name

Type

Language

PHENYLPROPANOLAMINE BITARTRATE

Common Name

English

(R*,S*)-(±)-.ALPHA.-(1-AMINOETHYL)BENZENEMETHANOL BITARTRATE

Systematic Name

English

Phenylpropanolamine bitartrate [WHO-DD]

Common Name

English

PHENYLPROPANOLAMINE BITARTRATE [USP IMPURITY]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C87053