PROPOXYPHENE

US Previously Marketed

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H29NO2
Molecular Weight	339.4712
Optical Activity	( + )
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=XLMALTXPSGQGBX-GCJKJVERSA-N

InChI=1S/C22H29NO2/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/t18-,22+/m1/s1

HIDE SMILES / InChI

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 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
Papillary necrosis mimicking staghorn calculi.	1982 Sep	6126946
Binding and hydrolysis of meperidine by human liver carboxylesterase hCE-1.	1999 Jul	10381793
Postoperative analgesia at home after ambulatory hand surgery: a controlled comparison of tramadol, metamizol, and paracetamol.	2001 Feb	11159230
Cocaine-like discriminative stimulus effects and [3H]dopamine uptake inhibition produced by selected partial opioid agonists.	2001 Jul	11548108
[Chronic pain in geriatrics].	2001 Jun	11488082
Bile analysis of drugs in postmortem cases.	2002 Aug 14	12208019
Acitretin-associated thrombotic stroke.	2002 Dec	12452748
Effects of intermediate- and long-term use of opioids on cognition in patients with chronic pain.	2002 Jul-Aug	12479258
Patient-controlled regional analgesia (PCRA) at home: controlled comparison between bupivacaine and ropivacaine brachial plexus analgesia.	2002 Jun	12170038
Safety of propoxyphene in dialysis patients.	2002 Sep-Oct	12358644
Transdermal clonidine: does it affect pain after abdominal hysterectomy?	2003	14598620
Demographics, assessment and management of pain in the elderly.	2003	12513114
[Di-Antalvic-induced esophageal ulcer].	2003 Apr	12759688
Drug- and mutagenesis-induced changes in the selectivity filter of a cardiac two-pore background K+ channel.	2003 Apr 1	12667945
Co-proxamol and suicide: Co-proxamol should be restricted, not banned.	2003 Aug 2	12896947
Co-proxamol and suicide: a study of national mortality statistics and local non-fatal self poisonings.	2003 May 10	12742920
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
CYP3A4 mediates dextropropoxyphene N-demethylation to nordextropropoxyphene: human in vitro and in vivo studies and lack of CYP2D6 involvement.	2004 Oct	15764408
Inappropriately defining "inappropriate medication for the elderly".	2004 Sep	15341569
Relation of postmortem blood alcohol and drug concentrations in fatal poisonings involving amitriptyline, propoxyphene and promazine.	2005 Aug	16138729
Usage of paracetamol-containing combination analgesics remains high in primary care.	2005 Dec	16305590
The role of tramadol in cancer pain treatment--a review.	2005 Jan	15668743
Acute pain management pharmacology for the patient with concurrent renal or hepatic disease.	2005 Jun	15973913
A randomized, double-blind, placebo controlled triphosphate in study of oral adenosine subacute low back pain.	2005 Jun	15940776
Are incorrectly used drugs more frequently involved in adverse drug reactions? A prospective study.	2005 May	15824914
Clinical toxicology: clinical science to public health.	2005 Nov	16405458
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
Profound metoprolol-induced bradycardia precipitated by acetaminophen-propoxyphene.	2006 Mar	16513452
Differential in vitro inhibition of M3G and M6G formation from morphine by (R)- and (S)-methadone and structurally related opioids.	2006 Mar	16487227
The occurrence of selected pharmaceuticals in wastewater effluent and surface waters of the lower Tyne catchment.	2006 Mar 1	15936058
Propoxyphene-induced hypoglycemia in renal failure.	2006 Mar-Apr	16690465

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 `Fri Dec 15 15:10:15 GMT 2023` Edited by `admin` on `Fri Dec 15 15:10:15 GMT 2023`
Record UNII	S2F83W92TK
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PROPOXYPHENE

Common Name

English

IDS-ND-004(SECT.2)

Code

English

J5.928E

Code

English

Dextropropoxyphene [WHO-DD]

Common Name

English

DEPROMIC

Common Name

English

PROPOXYPHENE [MI]

Common Name

English

D-PROPOXYPHENE

Common Name

English

DEXTROPROPOXYPHENE

Official Name

English

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

Systematic Name

English

PROPOXYPHENE [HSDB]

Common Name

English

PROPOXYPHENE, (+)-

Common Name

English

SK-65

Code

English

PROPOXYPHENE, D-

Common Name

English

dextropropoxyphene [INN]

Common Name

English

DEXTROPROPOXYPHENE [MART.]

Common Name

English

(+)-PROPOXYPHENE

Common Name

English

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

Common Name

English

PROPOXYPHENE [VANDF]

Common Name

English

DEXTROPROPOXYPHEN

Common Name

English

ALGAFAN

Common Name

English

Classification Tree Code System Code

WHO-ATC

N02AC04