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Identification
NameDextropropoxyphene
Accession NumberDB00647  (APRD00548)
TypeSmall Molecule
GroupsApproved, Illicit, Withdrawn
Description

Dextropropoxyphene is an analgesic in the opioid category, patented (1955) and manufactured by Eli Lilly and Company. It is intended to treat mild pain and also has antitussive and local anaesthetic effects. The drug has been taken off the market in Europe and the US due to concerns of fatal overdoses and heart arrhythmias. An estimated 10 million patients have used these products.

The drug is often referred to as the general form, “propoxyphene”, however only the dextro-isomer (dextropropoxyphene) has any analgesic effect. The levo-isomer appears to exhibit a very limited antitussive effect.

Structure
Thumb
Synonyms
SynonymLanguageCode
d-PropoxypheneNot AvailableNot Available
DestropropossifeneNot AvailableNot Available
DextropropoxifenoSpanishINN
DextropropoxyphenGermanINN
DextropropoxyphèneFrenchINN
DextropropoxyphenumLatinINN
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Darvon-ntablet, film coated100 mgoralStat Rx USA2009-09-25Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Propoxyphenecapsule65 mgoralStat Rx USA2009-10-27Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Propoxyphenecapsule65 mgoralPd Rx Pharmaceuticals, Inc.1973-06-20Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Propoxyphenecapsule65 mgoralPd Rx Pharmaceuticals, Inc.2010-05-10Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Over the Counter ProductsNot Available
International Brands
NameCompany
AbalginDLF
DacotonStandard
DarvonEli Lilly
DeprancolParke Davis
DepronalPfizer
DoleneNot Available
DoloxeneAspen Pharmacare
Brand mixtures
Brand NameIngredients
Balacetacetaminophen + dextropropoxyphene
Capadexacetaminophen + dextropropoxyphene
Darvocetacetaminophen + dextropropoxyphene
Di-Antalvicacetaminophen + dextropropoxyphene
Lentogesicacetaminophen + dextropropoxyphene
Paradexacetaminophen + dextropropoxyphene
Propacetacetaminophen + dextropropoxyphene
Salts
Name/CASStructureProperties
Dextropropoxyphene Hydrochloride
1639-60-7
Thumb
  • InChI Key: QMQBBUPJKANITL-MYXGOWFTSA-N
  • Monoisotopic Mass: 375.196506916
  • Average Mass: 375.932
DBSALT000500
Dextropropoxyphene Napsylate
ThumbNot applicableDBSALT001000
Categories
CAS number469-62-5
WeightAverage: 339.4712
Monoisotopic: 339.219829177
Chemical FormulaC22H29NO2
InChI KeyXLMALTXPSGQGBX-PEODTPIXNA-N
InChI
InChI=1/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+/s2
IUPAC Name
(2S,3R)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl propanoate
SMILES
CCC(=O)O[C@@](CC1=CC=CC=C1)([C@H](C)CN(C)C)C1=CC=CC=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassStilbenes
Sub ClassNot Available
Direct ParentStilbenes
Alternative Parents
Substituents
  • Stilbene
  • Phenylbutylamine
  • Phenylpropylamine
  • Benzyloxycarbonyl
  • Phenylpropane
  • Aralkylamine
  • Benzenoid
  • Monocyclic benzene moiety
  • Tertiary aliphatic amine
  • Tertiary amine
  • Carboxylic acid ester
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
  • 1-benzyl-3-(dimethylamino)-2-methyl-1-phenylpropyl propanoate (CHEBI:51173 )
Pharmacology
IndicationFor the relief of mild to moderate pain
PharmacodynamicsPropoxyphene, a synthetic opiate agonist, is structurally similar to methadone. Its general pharmacologic properties are those of the opiates as a group. The analgesic effect of propoxyphene is due to the d-isomer, dextropropoxyphene. It binds to the opiate receptors and leads to a decrease of the perception of pain stimuli. Propoxyphene possesses little to no antitussive activity and no antipyretic action.
Mechanism of actionPropoxyphene acts as a weak agonist at OP1, OP2, and OP3 opiate receptors within the central nervous system (CNS). Propoxyphene primarily affects OP3 receptors, which are coupled with G-protein receptors and function as modulators, both positive and negative, of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine, and noradrenaline is inhibited. Opioids such as propoxyphene also inhibit the release of vasopressin, somatostatin, insulin, and glucagon. Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). This results in hyperpolarization and reduced neuronal excitability.
AbsorptionNot Available
Volume of distribution
  • 16 L/kg
Protein bindingNot Available
Metabolism

Hepatic

Route of eliminationThe major route of metabolism is cytochrome CYP3A4 mediated N-demethylation to norpropoxyphene, which is excreted by the kidneys. In 48 hours, approximately 20% to 25% of the administered dose of propoxyphene is excreted via the urine, most of which is free or conjugated norpropoxyphene.
Half life6-12 hours
Clearance
  • 2.6 L/min
ToxicityComa, respiratory depression, circulatory collapse, and pulmonary edema. Seizures occur more frequently in patients with propoxyphene intoxication than in those with opiate intoxication. LD50=230mg/kg (orally in rat, Emerson)
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Propoxyphene Action PathwayDrug actionSMP00672
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.997
Blood Brain Barrier+0.9503
Caco-2 permeable+0.7277
P-glycoprotein substrateSubstrate0.5798
P-glycoprotein inhibitor IInhibitor0.7851
P-glycoprotein inhibitor IINon-inhibitor0.6469
Renal organic cation transporterNon-inhibitor0.6086
CYP450 2C9 substrateNon-substrate0.833
CYP450 2D6 substrateNon-substrate0.9117
CYP450 3A4 substrateSubstrate0.6032
CYP450 1A2 substrateInhibitor0.6357
CYP450 2C9 substrateNon-inhibitor0.7637
CYP450 2D6 substrateInhibitor0.6887
CYP450 2C19 substrateNon-inhibitor0.7628
CYP450 3A4 substrateNon-inhibitor0.7992
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.646
Ames testNon AMES toxic0.8896
CarcinogenicityCarcinogens 0.7164
BiodegradationNot ready biodegradable0.9714
Rat acute toxicity2.9360 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9033
hERG inhibition (predictor II)Inhibitor0.6837
Pharmacoeconomics
Manufacturers
  • Xanodyne pharmaceutics inc
  • Heritage pharmaceuticals inc
  • Mk laboratories inc
  • Halsey drug co inc
  • Alra laboratories inc
  • Impax laboratories inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Nexgen pharma inc
  • Par pharmaceutical inc
  • Purepac pharmaceutical co
  • Private formulations inc
  • Roxane laboratories inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Valeant pharmaceuticals international
  • Vintage pharmaceuticals inc
  • Watson laboratories inc
  • West ward pharmaceutical corp
  • Whiteworth towne paulsen inc
  • Warner chilcott div warner lambert co
  • Aaipharma llc
Packagers
Dosage forms
FormRouteStrength
Capsuleoral65 mg
Tablet, film coatedoral100 mg
Prices
Unit descriptionCostUnit
Propoxyphene napsylate powder5.33USD g
Darvon-n 100 mg tablet2.16USD tablet
Darvon 65 mg capsule1.71USD capsule
Propoxyphene N-APAP 100-500 mg tablet1.6USD tablet
Darvon 65 mg pulvule1.49USD each
Propoxyphene N-APAP 50-325 mg tablet1.32USD tablet
Propoxyphene-APAP 65-650 mg tablet0.57USD tablet
Propoxyphene N-APAP 100-650 mg tablet0.47USD tablet
Propoxyphene hcl 65 mg capsule0.43USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point75.5 °CPhysProp
water solubility3.32 mg/L (at 25 °C)MCFARLAND,JW ET AL. (2001)
logP4.18HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.00419 mg/mLALOGPS
logP4.06ALOGPS
logP4.9ChemAxon
logS-4.9ALOGPS
pKa (Strongest Basic)9.52ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area29.54 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity102.88 m3·mol-1ChemAxon
Polarizability38.86 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
References
Synthesis Reference

Carl R. White, “Synthesis and purification of d-propoxyphene hydrochloride.” U.S. Patent US4661625, issued April, 1973.

US4661625
General Reference
  1. Coda BA, Rudy AC, Archer SM, Wermeling DP: Pharmacokinetics and bioavailability of single-dose intranasal hydromorphone hydrochloride in healthy volunteers. Anesth Analg. 2003 Jul;97(1):117-23, table of contents. Pubmed
External Links
ATC CodesN02AC04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (46.1 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Mu-type opioid receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Mu-type opioid receptor P35372 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Ulens C, Daenens P, Tytgat J: Norpropoxyphene-induced cardiotoxicity is associated with changes in ion-selectivity and gating of HERG currents. Cardiovasc Res. 1999 Dec;44(3):568-78. Pubmed
  3. Tyers MB: A classification of opiate receptors that mediate antinociception in animals. Br J Pharmacol. 1980 Jul;69(3):503-12. Pubmed
  4. Picker MJ: Discriminative stimulus effects of the mixed-opioid agonist/antagonist dezocine: cross-substitution by mu and delta opioid agonists. J Pharmacol Exp Ther. 1997 Dec;283(3):1009-17. Pubmed
  5. Codd EE, Shank RP, Schupsky JJ, Raffa RB: Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception. J Pharmacol Exp Ther. 1995 Sep;274(3):1263-70. Pubmed
  6. Bannwarth B, Richez C: The dextropropoxyphene controversy. Joint Bone Spine. 2009 Oct;76(5):449-51. Epub 2009 Jul 14. Pubmed
  7. Walker EA, Tiano MJ, Benyas SI, Dykstra LA, Picker MJ: Naltrexone and beta-funaltrexamine antagonism of the antinociceptive and response rate-decreasing effects of morphine, dezocine, and d-propoxyphene. Psychopharmacology (Berl). 1999 May;144(1):45-53. Pubmed

2. Delta-type opioid receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Delta-type opioid receptor P41143 Details

References:

  1. Neil A: Affinities of some common opioid analgesics towards four binding sites in mouse brain. Naunyn Schmiedebergs Arch Pharmacol. 1984 Nov;328(1):24-9. Pubmed

3. Kappa-type opioid receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Kappa-type opioid receptor P41145 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Neil A: Affinities of some common opioid analgesics towards four binding sites in mouse brain. Naunyn Schmiedebergs Arch Pharmacol. 1984 Nov;328(1):24-9. Pubmed

Enzymes

1. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2C8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 3A7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 3A7 P24462 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on January 16, 2014 11:03