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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
Salts Not Available
Brand names
Name Company
Algafan
Antalvic
Darvon
Deprancol
Depromic
Dolene
Dolocap
Doloxen
Doloxene
Erantin
Femadol
Harmar
Kesso-Gesic
Propacet
Prophene 65
Propoxychel
Propoxyphene HCl 65
Proxagesic
First Prev Next Last
Brand 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-ZZWBGTBQSA-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/t18-,22?/m1/s1
Plain Text
IUPAC Name
(3R)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl propanoate
SMILES
CCC(=O)OC(CC1=CC=CC=C1)([C@H](C)CN(C)C)C1=CC=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
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
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 75.5 °C PhysProp
water solubility 3.32 mg/L (at 25 °C) MCFARLAND,JW ET AL. (2001)
logP 4.18 HANSCH,C ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 4.19e-03 g/l ALOGPS
logP 4.06 ALOGPS
logP 4.9 ChemAxon
logS -4.9 ALOGPS
pKa (strongest basic) 9.52 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 2 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 29.54 ChemAxon
rotatable bond count 9 ChemAxon
refractivity 102.88 ChemAxon
polarizability 38.4 ChemAxon
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
ChEBI 8497 Link_out
ChEMBL 8497 Link_out
Therapeutic Targets Database DAP000017 Link_out
PharmGKB PA451142 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
Drug Interaction
Acenocoumarol Propoxyphene may increase the anticoagulant effect of acenocoumarol.
Alvimopan Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Anisindione Propoxyphene may increase the anticoagulant effect of anisindione.
Atomoxetine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Carbamazepine Propoxyphene increases the effect of carbamazepine
Cimetidine Cimetidine, a moderate CYP3A4 inhibitor, may decrease the metabolism of propoxyphene. Monitor for changes in the therapeutic and adverse effects of propoxyphene if cimetidine is intitiated, discontinued or dose changed.
Dicumarol Propoxyphene may increase the anticoagulant effect of dicumarol.
Ritonavir Ritonavir increases the levels of analgesic
Tranylcypromine Increased risk of serotonin syndrome. Concomitant use should be avoided.
Triprolidine The CNS depressants, Triprolidine and Propoxyphene, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Warfarin Propoxyphene may increase the anticoagulant effect of warfarin.
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 February 08, 2013 16:19