PROPOXYPHENE HYDROCHLORIDE

US Previously Marketed

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H29NO2.ClH
Molecular Weight	375.932
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CCC(=O)O[C@@](CC1=CC=CC=C1)([C@H](C)CN(C)C)C2=CC=CC=C2

InChI

InChIKey=QMQBBUPJKANITL-MYXGOWFTSA-N

InChI=1S/C22H29NO2.ClH/c1-5-21(24)25-22(18(2)17-23(3)4,20-14-10-7-11-15-20)16-19-12-8-6-9-13-19;/h6-15,18H,5,16-17H2,1-4H3;1H/t18-,22+;/m1./s1

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C22H29NO2
Molecular Weight	339.4712
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016862s041s042lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/6151117 | https://www.ncbi.nlm.nih.gov/pubmed/21215785 | https://www.drugs.com/propoxyphene.html

Propoxyphene is a centrally acting opiate analgesic. Propoxyphene is an odorless, freely soluble in water, white crystalline powder with a bitter taste. In vitro studies demonstrated propoxyphene and the metabolite norpropoxyphene inhibit sodium channels (local anesthetic effect) with norpropoxyphene being approximately 2 fold more potent than propoxyphene and propoxyphene approximately 10 fold more potent than lidocaine. Propoxyphene and norpropoxyphene inhibit the voltage-gated potassium current carried by cardiac rapidly activating delayed rectifier (hERG) channels with approximately equal potency. It is unclear if the effects on ion channels occur within therapeutic dose range. Propoxyphene is indicated for the relief of mild to moderate pain.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Mu opioid receptor 231 Target ID: CHEMBL233 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6151117	Agonist 2752	53.0 nM [Kd]
Kappa opioid receptor 115 Target ID: CHEMBL237 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6151117	Antagonist 2849	140.0 nM [Kd]
Delta opioid receptor 81 Target ID: CHEMBL236 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6151117	Antagonist 2849	2100.0 nM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Mild to moderate pain 5 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016862s041s042lbl.pdf	Primary		Approved 8583	DARVON COMPOUND-65 Approved Use This product is indicated for the relief of mild to moderate pain, either when pain is present alone or when it is accompanied by fever. Launch Date 1957

C_max

Value	Dose	Co-administered	Analyte	Population
2310 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7391940/	7.5 mg/kg single, oral dose: 7.5 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		NORPROPOXYPHENE plasma	Canis lupus population: HEALTHY age: ADULT sex: MALE food status: FASTED
459 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7391940/	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		NORPROPOXYPHENE plasma	Canis lupus population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
126000 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7391940/	7.5 mg/kg single, oral dose: 7.5 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		NORPROPOXYPHENE plasma	Canis lupus population: HEALTHY age: ADULT sex: MALE food status: FASTED
2440 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7391940/	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		NORPROPOXYPHENE plasma	Canis lupus population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7391940/	7.5 mg/kg single, oral dose: 7.5 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		NORPROPOXYPHENE plasma	Canis lupus population: HEALTHY age: ADULT sex: MALE food status: FASTED
4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7391940/	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		NORPROPOXYPHENE plasma	Canis lupus population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
1700 mg 1 times / day multiple, oral Highest studied dose Dose: 1700 mg, 1 times / day Route: oral Route: multiple Dose: 1700 mg, 1 times / day Sources: https://www.tandfonline.com/doi/abs/10.1080/02791072.1974.10471830	unhealthy, 29 years Health Status: unhealthy Age Group: 29 years Sex: M Sources: https://www.tandfonline.com/doi/abs/10.1080/02791072.1974.10471830	Other AEs: Seizure... Other AEs: Seizure Sources: https://www.tandfonline.com/doi/abs/10.1080/02791072.1974.10471830
1000 mg 1 times / day multiple, oral Studied dose Dose: 1000 mg, 1 times / day Route: oral Route: multiple Dose: 1000 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/4847425/	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/4847425/	Disc. AE: Emesis, Blurred vision... Other AEs: Feeling detached, Dizziness... AEs leading to discontinuation/dose reduction: Emesis (3.1%) Blurred vision (3.1%) Other AEs: Feeling detached (12.5%) Dizziness (3.1%) Drowsiness (6.2%) Nervous (6.2%) Shaking (6.2%) Headaches (6.2%) Hangover (3.1%) Taste metallic (6.2%) Cramps leg (3.1%) Upset stomach (6.2%) Constipation (6.2%) Sources: https://pubmed.ncbi.nlm.nih.gov/4847425/
200 mg 1 times / day single, oral Studied dose Dose: 200 mg, 1 times / day Route: oral Route: single Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/4936999/	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/4936999/	Other AEs: Dizziness, Diaphoresis... Other AEs: Dizziness (grade 3, 4.2%) Diaphoresis (grade 3, 2.1%) Sources: https://pubmed.ncbi.nlm.nih.gov/4936999/
800 mg 1 times / day multiple, oral Studied dose Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: https://jamanetwork.com/journals/jama/article-abstract/351679	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: https://jamanetwork.com/journals/jama/article-abstract/351679	Other AEs: Dysphoria... Other AEs: Dysphoria (grade 1) Sources: https://jamanetwork.com/journals/jama/article-abstract/351679
800 mg 1 times / day multiple, oral Studied dose Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/805264/	unhealthy, mean age 28.5 years Health Status: unhealthy Age Group: mean age 28.5 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/805264/	Other AEs: Constipation, Delirium... Other AEs: Constipation Delirium Dysphoria Euphoria Sedation Sources: https://pubmed.ncbi.nlm.nih.gov/805264/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252		inhibitor 2507	inhibitor 2217 activator 14

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741 UGT2B4 23

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
UGT2B4 23	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/20484152/	major [Ki 3.5 uM]
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17962372/	yes [IC50 63.3 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/017122s061s062lbl.pdf	yes
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16513452/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/017122s061s062lbl.pdf	yes	yes (co-administration study) Comment: Propoxyphene inhibits CYP2D6-mediated hepatic clearance of metoprolol Sources: https://pubmed.ncbi.nlm.nih.gov/16513452/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/017122s061s062lbl.pdf

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15764408/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/017122s061s062lbl.pdf	yes

Tox targets

Target	Modality	Metabolite
hERG 2263	activator 14 Sources: https://pubmed.ncbi.nlm.nih.gov/10690289/
hERG 2263	activator 14 Sources: https://pubmed.ncbi.nlm.nih.gov/10690289/	NORPROPOXYPHENE 5
hERG 2263	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/10690289/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/017122s061s062lbl.pdf
hERG 2263	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/10690289/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/017122s061s062lbl.pdf	NORPROPOXYPHENE 5

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B1-00421	http://www.3bsc.com/index/pro_info.php?id=20633
ABI Chem	AC1L1F41
AN PharmaTech	AN-18686
BOC Sciences	17140-78-2	https://www.bocsci.com/propoxyphene-napsylate-cas-17140-78-2-item-60846.html
Chemieliva Pharmaceutical Co., Ltd	PBCM1212591
ChemMol	30105079	http://www.chemmol.com/chemmol/30105079.html
ChemMol	49411692	http://www.chemmol.com/chemmol/49411692.html
Hangzhou APIChem Technology	AC-16040
MuseChem	M088379	https://www.musechem.com/product/M088379.html
NovoSeek	28332
PubChem	28332	https://pubchem.ncbi.nlm.nih.gov/compound/28332
PubChem	45357585	https://pubchem.ncbi.nlm.nih.gov/compound/45357585
Smolecule	S574802	https://www.smolecule.com/products/s574802
Yuhao Chemical	XJ4340	http://www.chemyuhao.com/17140-78-2.html

PubMed

Title	Date	PubMed
Analgesic effect of electroacupuncture in postthoracotomy pain: a prospective randomized trial.	2006-06	16731125
Consumer group urges Food and Drug Administration to ban drug Darvon.	2006-06	16730316
Development of opioid formulations with limited diversion and abuse potential.	2006-06	16564141
Propoxyphene-induced hypoglycemia in renal failure.	2006-05-13	16690465
Survival after marked hyperlactaemia.	2006-05	16674643
The occurrence of selected pharmaceuticals in wastewater effluent and surface waters of the lower Tyne catchment.	2006-03-01	15936058
[Patterns of prescription and usage of triptans in Alsace (France): misuse is frequent and avoidable].	2006-03	16585890
Profound metoprolol-induced bradycardia precipitated by acetaminophen-propoxyphene.	2006-03	16513452
Differential in vitro inhibition of M3G and M6G formation from morphine by (R)- and (S)-methadone and structurally related opioids.	2006-03	16487227
Dextropropoxyphene combinations: Swedish market withdrawal.	2006-02	16548113
Time-trends in method-specific suicide rates compared with the availability of specific compounds. The Danish experience.	2006	16635927
Usage of paracetamol-containing combination analgesics remains high in primary care.	2005-12	16305590
[Over-the-counter paracetamol a common cause of poisoning among teenage girls. The Poison Control Center's report on analgesics poisoning].	2005-11-24	16302507
Clinical toxicology: clinical science to public health.	2005-11	16405458
Bupivacaine/ketamine is superior to intra-articular ketamine analgesia following arthroscopic knee surgery.	2005-10	16189335
National trends in and predictors of propoxyphene use in community-dwelling older adults.	2005-09	16257821
Pain and pain treatments in European palliative care units. A cross sectional survey from the European Association for Palliative Care Research Network.	2005-09	16218160
Relation of postmortem blood alcohol and drug concentrations in fatal poisonings involving amitriptyline, propoxyphene and promazine.	2005-08	16138729
Paracetamol + dextropropoxyphene: planned withdrawal from the British market.	2005-08	16108102
In the days of patients' choice, why is the patient being ignored?	2005-07-26	16039322
Acute pain management pharmacology for the patient with concurrent renal or hepatic disease.	2005-06	15973913
A randomized, double-blind, placebo controlled triphosphate in study of oral adenosine subacute low back pain.	2005-06	15940776
Are incorrectly used drugs more frequently involved in adverse drug reactions? A prospective study.	2005-05	15824914
Co-proxamol and suicide: preventing the continuing toll of overdose deaths.	2005-03	15728397
Impact of paracetamol pack size restrictions on poisoning from paracetamol in England and Wales: an observational study.	2005-03	15637104
'Opioid poisoning deaths in New Zealand (2001-2002)' and the UK's recent decision to withdraw the pain killer coproxamol.	2005-02-11	15711627
Opioid poisoning deaths in New Zealand (2001-2002).	2005-02-11	15711626
A multicentre study of coproxamol poisoning suicides based on coroners' records in England.	2005-02	15676043
The role of tramadol in cancer pain treatment--a review.	2005-01	15668743
The impact of P-glycoprotein on the disposition of drugs targeted for indications of the central nervous system: evaluation using the MDR1A/1B knockout mouse model.	2005-01	15502009
Drug therapy in dental practice: nonopioid and opioid analgesics.	2005	16596914
Intermittent injection of bupivacaine into the margin or the cavity after reduction mammaplasty.	2005	16208784
Prevalence of opioid adverse events in chronic non-malignant pain: systematic review of randomised trials of oral opioids.	2005	16207320
ECG abnormalities in co-proxamol (paracetamol/dextropropoxyphene) poisoning.	2005	16035201
Dextropropoxyphene: safety and efficacy in older patients.	2005	15903354
Simultaneous determination of paracetamol and dextropropoxyphene in human plasma by liquid chromatography/tandem mass spectrometry: application to clinical bioequivalence studies.	2005	15714600
Investigating the environmental transport of human pharmaceuticals to streams in the United Kingdom.	2004-10-15	15364527
CYP3A4 mediates dextropropoxyphene N-demethylation to nordextropropoxyphene: human in vitro and in vivo studies and lack of CYP2D6 involvement.	2004-10	15764408
Evaluation of the Triage PPY on-site testing device for the detection of dextropropoxyphene in urine.	2004-09	15516300
Urine concentrations of fentanyl and norfentanyl during application of Duragesic transdermal patches.	2004-09	15516290
Criteria for prescribing require further study.	2004-09	15341570
Inappropriately defining "inappropriate medication for the elderly".	2004-09	15341569
The occurrence of selected human pharmaceutical compounds in UK estuaries.	2004-09	15325211
Propoxyphene use in the elderly.	2004-07	15209680
[Plasma assay of methadone enantiomers with high performance liquid chromatography].	2004-05	15243353
Improvement of pain treatment after major abdominal surgery by intravenous S+-ketamine.	2004-05	15105223
Titanium pigment in tissues of drug addicts: report of 5 necropsied cases.	2004-04	15122423
Self-reported drug use and urinalysis results.	2004-01	15270376
Potentially inappropriate prescribing in Canada relative to the US.	2004	15554752
30-MINUTES-TUMT. Use of the visual analogue scale to investigate patients' pain perception, different cocktail options and tolerability during 30 minutes' treatment.	2004	15331897

Patents

Sample Use Guides

In Vivo Use Guide

Darvon-N (Propoxyphene) is given orally. The usual dosage is one 100 mg propoxyphene napsylate tablet every 4 hours as needed for pain. The maximum dose of Darvon-N is 6 tablets per day. Do not exceed the maximum daily dose.

Route of Administration: Oral

In Vitro Use Guide

Cell membrane preparation (Chemiscreen™ MOR) expressing recombinant human MOR were used for activity evaluation. The assays were performed in microtiter plates with 40 mkL of binding buffer or Propoxyphene (1–100,000 mkM), 10 mkL of radioligand (2 nM (3H)-DAMG), and 50 mkL of diluted membranes with three wells per group. The plates were then incubated at room temperature for 2h. The binding incubation was terminated by the addition of 100 mkL cold binding buffer to each well. The glass fiber filter plates were presoaked for 30–45 min with 0.33% PEI buffer. The PEI solution was removed from the filter plate with a vacuum manifold (Millipore) and the filters washed with 200 mkL priming buffer (50 mM HEPES, 0.5% BSA, pH 7.4) per well. The binding reaction was transferred to the filter plate and washed with 200 mkL washing buffer (50 mM HEPES with 500 mM NaCl and 0.1% BSA, pH 7.4).

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:46:04 GMT 2025` Edited by `admin` on `Mon Mar 31 17:46:04 GMT 2025`
Record UNII	CB2TL9PS0T
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PROPOXYPHENE HYDROCHLORIDE

Official Name

English

DEXTROPROPOXYPHENE HYDROCHLORIDE

Preferred Name

English

DOLENE AP-65 COMPONENT PROPOXYPHENE HYDROCHLORIDE

Common Name

English

DARVON

Brand Name

English

FEMADOL

Common Name

English

PROPOXYPHENE HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

PROPOXYPHENE HYDROCHLORIDE [USAN]

Common Name

English

DARVON COMPOUND COMPONENT PROPOXYPHENE HYDROCHLORIDE

Common Name

English

PROPOXYPHENE HYDROCHLORIDE [USP IMPURITY]

Common Name

English

DARVOCET COMPONENT PROPOXYPHENE HYDROCHLORIDE

Common Name

English

HARMAR

Common Name

English

DOLENE

Brand Name

English

PROPOXYPHENE HYDROCHLORIDE CII

Common Name

English

Dextropropoxyphene hydrochloride [WHO-DD]

Common Name

English

PROPOXYPHENE HYDROCHLORIDE [VANDF]

Common Name

English

(2S,3R)-(+)-4-(DIMETHYLAMINO)-3-METHYL-1,2-DIPHENYL-2-BUTANOL PROPIONATE (ESTER) HYDROCHLORIDE

Common Name

English

DEXTROPROPOXYPHENE HYDROCHLORIDE [EP MONOGRAPH]

Common Name

English

PROPOXYPHENE HCL

Common Name

English

KESSO-GESIC

Brand Name

English

PROPHENE 65

Brand Name

English

BENZENEETHANOL, .ALPHA.-(2-(DIMETHYLAMINO)-1-METHYLETHYL)-.ALPHA.-PHENYL-, PROPANOATE (ESTER), HYDROCHLORIDE, (S-(R*,S*))-

Common Name

English

DEPRANCOL

Common Name

English

DEXTROPROPOXYPHENE HYDROCHLORIDE [MART.]

Common Name

English

WYGESIC COMPONENT PROPOXYPHENE HYDROCHLORIDE

Common Name

English

PROXAGESIC

Common Name

English

PROPOXYPHENE HYDROCHLORIDE [MI]

Common Name

English

ALGAPHAN

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C67413