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

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 221 Target ID: CHEMBL233 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6151117	Agonist 2678	53.0 nM [Kd]
Kappa opioid receptor 108 Target ID: CHEMBL237 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6151117	Antagonist 2778	140.0 nM [Kd]
Delta opioid receptor 77 Target ID: CHEMBL236 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6151117	Antagonist 2778	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 8429	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 n = 1 Health Status: unhealthy Condition: heroin dependence Age Group: 29 years Sex: M Population Size: 1 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 (mean) 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 n = 32 Health Status: unhealthy Condition: heroin and methadone dependence Age Group: adult Sex: M+F Population Size: 32 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 n = 48 Health Status: unhealthy Condition: pain Age Group: adult Sex: M+F Population Size: 48 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 (mean) 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 n = 272 Health Status: unhealthy Condition: heroin dependence Age Group: adult Sex: M+F Population Size: 272 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 (starting) 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 n = 32 Health Status: unhealthy Condition: heroin dependence Age Group: mean age 28.5 years Sex: M+F Population Size: 32 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 1737 inhibitor 1587		inhibitor 1852	inhibitor 1612 activator 14

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 UGT2B4 19

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
UGT2B4 19	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20484152/	major [Ki 3.5 uM]
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17962372/	yes [IC50 63.3 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/017122s061s062lbl.pdf	yes
CYP2D6 1891	inhibitor 3277 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 1737	substrate 3367 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 1647	activator 14 Sources: https://pubmed.ncbi.nlm.nih.gov/10690289/
hERG 1647	activator 14 Sources: https://pubmed.ncbi.nlm.nih.gov/10690289/	NORPROPOXYPHENE 5
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/10690289/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/017122s061s062lbl.pdf
hERG 1647	inhibitor 1626 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
ChemMol	30105079	http://www.chemmol.com/chemmol/30105079.html
ChemMol	49411692	http://www.chemmol.com/chemmol/49411692.html
Chemieliva Pharmaceutical Co., Ltd	PBCM1212591
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
The apomorphine test: a biological marker for heroin dependence disorder?	2002 Oct	14578019
Accidental dextropropoxyphene poisoning.	2003 Apr	12793316
[Di-Antalvic-induced esophageal ulcer].	2003 Apr	12759688
Summary version of the Standards, Options and Recommendations for the use of analgesia for the treatment of nociceptive pain in adults with cancer (update 2002).	2003 Aug	12915905
Propoxyphene use by community-dwelling and institutionalized elderly Medicare beneficiaries.	2003 Aug	12890072
Co-proxamol and suicide: Licence needs to be changed.	2003 Aug 2	12896949
Co-proxamol and suicide: Availability of co-proxamol has been successfully reduced in Doncaster.	2003 Aug 2	12896948
Sustained modelling ability of artificial neural networks in the analysis of two pharmaceuticals (dextropropoxyphene and dipyrone) present in unequal concentrations.	2003 Jul	12802564
Co-proxamol and suicide: a study of national mortality statistics and local non-fatal self poisonings.	2003 May 10	12742920
Dependence on legal psychotropic drugs among alcoholics.	2003 Nov-Dec	14633651
[Impact of 2 strategies of analgesia on postoperative pain after emergency hand surgery performed on an ambulatory basis].	2003 Oct	14522387
Determination of selected human pharmaceutical compounds in effluent and surface water samples by high-performance liquid chromatography-electrospray tandem mass spectrometry.	2003 Oct 10	14570326
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
Titanium pigment in tissues of drug addicts: report of 5 necropsied cases.	2004 Apr	15122423
Patterns and trends in opioid use among individuals with back pain in the United States.	2004 Apr 15	15082989
Weak opiate analgesics: modest practical merits.	2004 Feb	15055224
Self-reported drug use and urinalysis results.	2004 Jan	15270376
Propoxyphene use in the elderly.	2004 Jul	15209680
A population-based study of pain and quality of life during the year before death in men with prostate cancer.	2004 Mar 22	15026796
[Plasma assay of methadone enantiomers with high performance liquid chromatography].	2004 May	15243353
Improvement of pain treatment after major abdominal surgery by intravenous S+-ketamine.	2004 May	15105223
CYP3A4 mediates dextropropoxyphene N-demethylation to nordextropropoxyphene: human in vitro and in vivo studies and lack of CYP2D6 involvement.	2004 Oct	15764408
Evaluation of the Triage PPY on-site testing device for the detection of dextropropoxyphene in urine.	2004 Sep	15516300
Urine concentrations of fentanyl and norfentanyl during application of Duragesic transdermal patches.	2004 Sep	15516290
Criteria for prescribing require further study.	2004 Sep	15341570
Inappropriately defining "inappropriate medication for the elderly".	2004 Sep	15341569
The occurrence of selected human pharmaceutical compounds in UK estuaries.	2004 Sep	15325211
Intermittent injection of bupivacaine into the margin or the cavity after reduction mammaplasty.	2005	16208784
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
'Opioid poisoning deaths in New Zealand (2001-2002)' and the UK's recent decision to withdraw the pain killer coproxamol.	2005 Feb 11	15711627
Opioid poisoning deaths in New Zealand (2001-2002).	2005 Feb 11	15711626
In the days of patients' choice, why is the patient being ignored?	2005 Jul 23-29	16039322
A randomized, double-blind, placebo controlled triphosphate in study of oral adenosine subacute low back pain.	2005 Jun	15940776
Co-proxamol and suicide: preventing the continuing toll of overdose deaths.	2005 Mar	15728397
Impact of paracetamol pack size restrictions on poisoning from paracetamol in England and Wales: an observational study.	2005 Mar	15637104
Clinical toxicology: clinical science to public health.	2005 Nov	16405458
Bupivacaine/ketamine is superior to intra-articular ketamine analgesia following arthroscopic knee surgery.	2005 Oct	16189335
Pain and pain treatments in European palliative care units. A cross sectional survey from the European Association for Palliative Care Research Network.	2005 Sep	16218160
Drug therapy in dental practice: nonopioid and opioid analgesics.	2005 Winter	16596914
Time-trends in method-specific suicide rates compared with the availability of specific compounds. The Danish experience.	2006	16635927
Dextropropoxyphene combinations: Swedish market withdrawal.	2006 Feb	16548113
Analgesic effect of electroacupuncture in postthoracotomy pain: a prospective randomized trial.	2006 Jun	16731125
Consumer group urges Food and Drug Administration to ban drug Darvon.	2006 Jun	16730316
Development of opioid formulations with limited diversion and abuse potential.	2006 Jun	16564141
[Patterns of prescription and usage of triptans in Alsace (France): misuse is frequent and avoidable].	2006 Mar	16585890
Differential in vitro inhibition of M3G and M6G formation from morphine by (R)- and (S)-methadone and structurally related opioids.	2006 Mar	16487227
Propoxyphene-induced hypoglycemia in renal failure.	2006 Mar-Apr	16690465
Survival after marked hyperlactaemia.	2006 May	16674643

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).

Name

Type

Language

PROPOXYPHENE HYDROCHLORIDE

Official Name

English

DOLENE AP-65 COMPONENT PROPOXYPHENE HYDROCHLORIDE

Common Name

English

DARVON

Brand Name

English

FEMADOL

Common Name

English

PROPOXYPHENE HYDROCHLORIDE COMPONENT OF DARVON COMPOUND

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 COMPONENT OF DARVOCET

Common 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

PROPOXYPHENE HYDROCHLORIDE COMPONENT OF WYGESIC

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

PROPOXYPHENE HYDROCHLORIDE COMPONENT OF DOLENE AP-65

Common Name

English

DEPRANCOL

Common Name

English

DEXTROPROPOXYPHENE HYDROCHLORIDE [MART.]

Common Name

English

WYGESIC COMPONENT PROPOXYPHENE HYDROCHLORIDE

Common Name

English

PROXAGESIC

Common Name

English

DEXTROPROPOXYPHENE HYDROCHLORIDE

Common Name

English

PROPOXYPHENE HYDROCHLORIDE [MI]

Common Name

English

ALGAPHAN

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C67413