Banner
targets (3) enzymes (5)
for drugs
Identification
Name Propoxyphene
Accession Number DB00647 (APRD00548)
Type small molecule
Groups illicit, approved
Description

A narcotic analgesic structurally related to methadone. Only the dextro-isomer has an analgesic effect; the levo-isomer appears to exert an antitussive effect. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • D-Propoxyphene
  • Dextropropoxyphene
  • Dextropropoxyphene-M
  • Dextroproxifeno
  • Propoxyphene HCl
Brand names
  • Algafan
  • Antalvic
  • Darvon
  • Darvon-N
  • Deprancol
  • Depromic
  • Dolene
  • Dolocap
  • Doloxen
  • Doloxene
  • Erantin
  • Femadol
  • Harmar
  • Kesso-Gesic
  • Propacet
  • Prophene 65
  • Propoxychel
  • Propoxyphene HCl 65
  • Proxagesic
Brand name mixtures Not Available
Categories
  • Narcotics
  • Analgesics
  • Antitussives
  • Analgesics, Opioid
CAS number 469-62-5
Weight Average: 339.4712
Monoisotopic: 339.219829177
Chemical Formula C22H29NO2
InChI Key InChIKey=XLMALTXPSGQGBX-UHFFFAOYSA-N
InChI
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
Plain Text
IUPAC Name
4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl propanoate
SMILES
CCC(=O)OC(CC1=CC=CC=C1)(C(C)CN(C)C)C1=CC=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Stilbenes
Substructures
  • Carboxylic Acids and Derivatives
  • Benzyl Alcohols and Derivatives
  • Acetates
  • Ethers
  • Benzene and Derivatives
  • Benzyl Esters
  • Benzylacetates
  • Cumenes and Derivatives
  • Stilbenes
  • Aliphatic and Aryl Amines
  • Aromatic compounds
  • Phenylpropylamines
Pharmacology
Indication For the relief of mild to moderate pain
Pharmacodynamics Propoxyphene, 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 action Propoxyphene 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.
Absorption Not Available
Volume of distribution
  • 16 L/kg
Protein binding Not Available
Metabolism

Hepatic
Route of elimination The 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 life 6-12 hours
Clearance
  • 2.6 L/min
Toxicity Coma, 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 Not Available
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
Form Route Strength
Capsule Oral
Prices
Unit description Cost Unit
Propoxyphene napsylate powder 5.33 USD g
Darvon-n 100 mg tablet 2.16 USD tablet
Darvon 65 mg capsule 1.71 USD capsule
Propoxyphene N-APAP 100-500 mg tablet 1.6 USD tablet
Darvon 65 mg pulvule 1.49 USD each
Propoxyphene N-APAP 50-325 mg tablet 1.32 USD tablet
Propoxyphene-APAP 65-650 mg tablet 0.57 USD tablet
Propoxyphene N-APAP 100-650 mg tablet 0.47 USD tablet
Propoxyphene hcl 65 mg capsule 0.43 USD capsule
Patents Not Available
Properties
State solid
Melting point 75-76oC
Experimental Properties
Property Value Source
water solubility 19.6mg/L PhysProp
logP 4.4 PhysProp
Predicted Properties
Property Value Source
water solubility 4.19e-03 g/l ALOGPS
logP 4.06 ALOGPS
logP 4.90 ChemAxon Molconvert
logS -4.91 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 2 ChemAxon Molconvert
hydrogen donor count 0 ChemAxon Molconvert
polar surface area 29.54 ChemAxon Molconvert
rotatable bond count 9 ChemAxon Molconvert
refractivity 102.88 ChemAxon Molconvert
polarizability 38.67 ChemAxon Molconvert
References
Synthesis Reference Not Available
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
Resource Link
KEGG Compound C07406 Link_out
PubChem Compound 15330 Link_out
PubChem Substance 46506690 Link_out
ChemSpider 14592 Link_out
ChEBI 8497 Link_out
ChEMBL 8497 Link_out
Therapeutic Targets Database DAP000017 Link_out
PharmGKB PA451142 Link_out
Drug Product Database 0 Link_out
RxList http://www.rxlist.com/cgi/generic/propox.htm Link_out
Drugs.com http://www.drugs.com/propoxyphene.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Propoxyphene Link_out
ATC Codes
  • N02AC04
  • N02AC54
  • N02AC74
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (46.1 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Take without regard to meals. Avoid alcohol.
Targets

1. Mu-type opioid receptor

Pharmacological action: yes
Actions: agonist

Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for beta-endorphin

Organism class: human
UniProt ID: P35372 Link_out
Gene: OPRM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: agonist

Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Highly stereoselective. receptor for enkephalins

Organism class: human
UniProt ID: P41143 Link_out
Gene: OPRD1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: antagonist

Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for dynorphins. May play a role in arousal and regulation of autonomic and neuroendocrine functions

Organism class: human
UniProt ID: P41145 Link_out
Gene: OPRK1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 3A4

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 2D6

Actions: inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:05

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.