Propoxyphene (CED0005127)

Record Information

Version

1.0

Creation Date

2009-07-21 20:27:20 UTC

Update Date

2026-05-14 16:44:59 UTC

SynCED ID

CED0005127

Secondary Accession Numbers

CHEM002237
T3D2848

Identification

Common Name

Propoxyphene

Class

Small Molecule

Description

Propoxyphene is an exogenous compound with the formula C22H29NO2 and an average molecular weight of 339.48 g/mol. It exists as a solid at room temperature. Propoxyphene belongs to the stilbenes, a class of phenylpropanoids and polyketides within the organic compounds. It is used as an opioid analgesic and mu-opioid receptor agonist, sourced from healthcare, pharmaceuticals, and veterinary products. The recorded route of exposure is oral. The compound targets several proteins, acting as an antagonist of Glutamate receptor ionotropic NMDA 1 (GRIN1), NMDA 2A (GRIN2A), NMDA 2D (GRIN2D), and NMDA 3B (GRIN3B), as well as three other proteins. Additionally, propoxyphene acts as a weak agonist at OP1, OP2, and OP3 opiate receptors within the central nervous system (CNS), including the Mu-type (OPRM1), Delta-type (OPRD1), and Kappa-type (OPRK1) opioid receptors. It 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.

Contaminant Type

Amine
Analgesic
Analgesic, Opioid
Antitussive Agent
Drug
Ester
Ether
Metabolite
Narcotic
Organic Compound
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
(-)-4-(Dimethylamino)-3-methyl-1,2-diphenyl-2-(propionyloxy)butane	ChEBI
(-)-Propoxyphene	ChEBI
(R)-alpha-(2-(Dimethylamino)-1-methylethyl)-alpha-phenylbenzeneethanol propanoate	ChEBI
L-Propoxyphene	ChEBI
Levopropossifene	ChEBI
Levopropoxifeno	ChEBI
Levopropoxyphenum	ChEBI
(R)-a-(2-(Dimethylamino)-1-methylethyl)-a-phenylbenzeneethanol propanoate	Generator
(R)-a-(2-(Dimethylamino)-1-methylethyl)-a-phenylbenzeneethanol propanoic acid	Generator
(R)-alpha-(2-(Dimethylamino)-1-methylethyl)-alpha-phenylbenzeneethanol propanoic acid	Generator
(R)-Α-(2-(dimethylamino)-1-methylethyl)-α-phenylbenzeneethanol propanoate	Generator
(R)-Α-(2-(dimethylamino)-1-methylethyl)-α-phenylbenzeneethanol propanoic acid	Generator
Levopropoxyphene	MeSH
Propoxyphene hydrochloride, (r,s)-(+-)-isomer	MeSH
Propoxyphene, (r,s)-(+-)-isomer	MeSH
Propoxyphene, (R-(r,s))-isomer	MeSH

Chemical Formula

C₂₂H₂₉NO₂

Average Molecular Mass

339.479 g/mol

Monoisotopic Mass

339.220 g/mol

CAS Registry Number

469-62-5

IUPAC Name

(2R,3S)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl propanoate

Traditional Name

levopropoxyphene

SMILES

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

InChI Identifier

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+/m0/s1

InChI Key

XLMALTXPSGQGBX-PGRDOPGGSA-N

Chemical Taxonomy

Description

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.

Kingdom

Organic compounds

Super Class

Phenylpropanoids and polyketides

Class

Stilbenes

Sub Class

Not Available

Direct Parent

Stilbenes

Alternative Parents

Substituents

Stilbene
Phenylbutylamine
Benzyloxycarbonyl
Phenylpropane
Aralkylamine
Monocyclic benzene moiety
Benzenoid
Tertiary aliphatic amine
Tertiary amine
Carboxylic acid ester
Amino acid or derivatives
Monocarboxylic acid or derivatives
Carboxylic acid derivative
Organic oxide
Organopnictogen compound
Organic oxygen compound
Organooxygen compound
Organonitrogen compound
Carbonyl group
Organic nitrogen compound
Amine
Hydrocarbon derivative
Aromatic homomonocyclic compound

Molecular Framework

Aromatic homomonocyclic compounds

External Descriptors

Not Available

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Applications

Biological Roles

Chemical Roles

Not Available

Organoleptic Effects

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	75.5°C
Boiling Point	Not Available
Solubility	3.32 mg/L (at 25°C)

Predicted Properties

Property	Value	Source
Water Solubility	0.0042 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 Å²	ChemAxon
Rotatable Bond Count	9	ChemAxon
Refractivity	102.88 m³·mol⁻¹	ChemAxon
Polarizability	38.92 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-052f-5097000000-14ee532e398ad87fafa7	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-0aor-7391000000-99df9afa035ec5903954	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-0a4l-9650000000-250ef3abb6af95e8d3b3	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-000i-3059000000-8b5a0ccf0362c5cb5fab	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-0540-5194000000-be7207ca388dafc238ca	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-0pb9-9270000000-ca80d8ae975fd75212c7	Not Available	View Spectrum

Toxicity Profile

Toxicity Values

Toxicity Value	Organism	Dose Descriptor	Route of Exposure	Predicted or Experimental	Toxicity Rating	Reference
230.0 mg/kg	rat	LD50	oral	experimental	Not Available	Not Available
193.0 Log mg/kg [100:340]	Rat	LD50	oral	predicted	Not Available	Not Available

Toxicity / Toxin Class

Not Available

Mechanism of Toxicity

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.

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Minimum Risk Level

Not Available

Symptoms

Coma, respiratory depression, circulatory collapse, and pulmonary edema. Seizures occur more frequently in patients with propoxyphene intoxication than in those with opiate intoxication.

Treatment

Attention should be directed first to establishing a patent airway and to restoring ventilation. Mechanically assisted ventilation, with or without oxygen, may be required, and positive pressure respiration may be desirable if pulmonary edema is present. The narcotic antagonist naloxone will markedly reduce the degree of respiratory depression, and 0.4 to 2 mg should be administered promptly, preferably intravenously. If the desired degree of counteraction with improvement in respiratory functions is not obtained, naloxone should be repeated at 2- to 3-minute intervals. The duration of action of the antagonist may be brief. If no response is observed after 10 mg of naloxone have been administered, the diagnosis of propoxyphene toxicity should be questioned. Naloxone may also be administered by continuous intravenous infusion. (3)

Health Effects

Health Effect	Relationship	Direction	Description	Reference

Exposure Sources

Source ID	Source	Sector	Reference
CEDs000370	Analgesics?Analgesics are a class of synthetic chemicals designed to alleviate pain.	Healthcare, pharmaceuticals & veterinary products	Not Available
CEDs000518	Electrically Stimulated Smoking Devices?Electrically stimulated smoking devices, commonly known as e-cigarettes or vape pens, utilize electrical components to heat a liquid solution, often containing nicotine, flavorings, and other additives, to produce an aerosol for inhalation.	Electrical & Electronic Equipment	PubChem
CEDs000580	Manufacture Preparation Of Tobacco Products?The manufacture and preparation of tobacco products involve various processes that can result in the introduction of synthetic chemicals into the environment.	Industrial manufacturing & chemical processing	PubChem
CEDs000632	Apparel?Apparel production often involves the use of various synthetic chemicals, including dyes, finishing agents, and preservatives.	Textiles, leather & furnishings	PubChem
CEDs000696	Nanotechnology?Nanotechnology involves the manipulation of materials at the molecular or atomic level, typically within the range of 1 to 100 nanometers.	Industrial manufacturing & chemical processing	PubChem

Pathways

1 pathwayPathway Source: PathBank

Propoxyphene Action Pathway

Targets

Structure	Protein	UniProt ID	Organism	Relationship	Details
Click to view 3D structure	Mu-type opioid receptor	P35372	Humans	Predicted (SEA)	Prediction Confidence Score 0.303 Applicability Domain 0.385 Statistical Significance 0.0678 Supporting Reference Compounds 527 E-value 528.207
Click to view 3D structure	Procathepsin L	P07711	Humans	Predicted (SEA)	Prediction Confidence Score 0.293 Applicability Domain 0.317 Statistical Significance 0.0314 Supporting Reference Compounds 167 E-value 244.68
Click to view 3D structure	Protein-glutamine gamma-glutamyltransferase	Q7M0F8	Cavia porcellus	Predicted (SEA)	Prediction Confidence Score 0.292 Applicability Domain 0.309 Statistical Significance 9.60e-04 Supporting Reference Compounds 2 E-value 7.47353
Click to view 3D structure	Cathepsin K	P43235	Humans	Predicted (SEA)	Prediction Confidence Score 0.289 Applicability Domain 0.317 Statistical Significance 0.0273 Supporting Reference Compounds 129 E-value 212.84
Click to view 3D structure	Delta-type opioid receptor	P41143	Humans	Predicted (SEA)	Prediction Confidence Score 0.287 Applicability Domain 0.385 Statistical Significance 0.0721 Supporting Reference Compounds 427 E-value 561.215
Click to view 3D structure	Voltage-gated inwardly rectifying potassium channel KCNH2	Q12809	Humans	Predicted (SEA)	Prediction Confidence Score 0.284 Applicability Domain 0.385 Statistical Significance 0.2395 Supporting Reference Compounds 1498 E-value 1864.8
Click to view 3D structure	Sigma non-opioid intracellular receptor 1	Q99720	Humans	Predicted (SEA)	Prediction Confidence Score 0.284 Applicability Domain 0.306 Statistical Significance 0.0887 Supporting Reference Compounds 562 E-value 690.445
Click to view 3D structure	Cathepsin S	P25774	Humans	Predicted (SEA)	Prediction Confidence Score 0.281 Applicability Domain 0.29 Low confidence Statistical Significance 0.0301 Supporting Reference Compounds 141 E-value 234.56
Click to view 3D structure	Cathepsin B	P07858	Humans	Predicted (SEA)	Prediction Confidence Score 0.281 Applicability Domain 0.317 Statistical Significance 0.0385 Supporting Reference Compounds 173 E-value 299.642
Click to view 3D structure	Muscarinic acetylcholine receptor M2	P08172	Humans	Predicted (SEA)	Prediction Confidence Score 0.281 Applicability Domain 0.304 Statistical Significance 0.0486 Supporting Reference Compounds 373 E-value 378.503
Click to view 3D structure	Peptidyl-glycine alpha-amidating monooxygenase	P19021	Humans	Predicted (SEA)	Prediction Confidence Score 0.281 Applicability Domain 0.281 Low confidence Statistical Significance 0.0084 Supporting Reference Compounds 1 E-value 65.3933
Click to view 3D structure	Kappa-type opioid receptor	P41145	Humans	Predicted (SEA)	Prediction Confidence Score 0.279 Applicability Domain 0.385 Statistical Significance 0.1005 Supporting Reference Compounds 532 E-value 782.774
Click to view 3D structure	D(3) dopamine receptor	P35462	Humans	Predicted (SEA)	Prediction Confidence Score 0.278 Applicability Domain 0.385 Statistical Significance 0.1182 Supporting Reference Compounds 861 E-value 920.567
Click to view 3D structure	Pancreatic alpha-amylase	P00689	Rattus norvegicus	Predicted (SEA)	Prediction Confidence Score 0.277 Applicability Domain 0.304 Statistical Significance 5.20e-04 Supporting Reference Compounds 2 E-value 4.04816
Click to view 3D structure	Mu-type opioid receptor	P33535	Rattus norvegicus	Predicted (SEA)	Prediction Confidence Score 0.277 Applicability Domain 0.313 Statistical Significance 0.0572 Supporting Reference Compounds 229 E-value 445.064
Click to view 3D structure	Muscarinic acetylcholine receptor M1	P11229	Humans	Predicted (SEA)	Prediction Confidence Score 0.276 Applicability Domain 0.304 Statistical Significance 0.062 Supporting Reference Compounds 385 E-value 482.977
Click to view 3D structure	Muscarinic acetylcholine receptor M3	P20309	Humans	Predicted (SEA)	Prediction Confidence Score 0.276 Applicability Domain 0.304 Statistical Significance 0.0466 Supporting Reference Compounds 310 E-value 362.855
Click to view 3D structure	Muscarinic acetylcholine receptor M4	P08173	Humans	Predicted (SEA)	Prediction Confidence Score 0.276 Applicability Domain 0.304 Statistical Significance 0.0456 Supporting Reference Compounds 297 E-value 354.681
Click to view 3D structure	Pol polyprotein	Q72874	Human immunodeficiency virus 1	Predicted (SEA)	Prediction Confidence Score 0.275 Applicability Domain 0.362 Statistical Significance 0.0138 Supporting Reference Compounds 54 E-value 107.432
Click to view 3D structure	Sigma non-opioid intracellular receptor 1	Q60492	Cavia porcellus	Predicted (SEA)	Prediction Confidence Score 0.273 Applicability Domain 0.313 Statistical Significance 0.0638 Supporting Reference Compounds 229 E-value 497.067
Click to view 3D structure	ATP-dependent translocase ABCB1	P08183	Humans	Predicted (SEA)	Prediction Confidence Score 0.273 Applicability Domain 0.385 Statistical Significance 0.0454 Supporting Reference Compounds 139 E-value 353.202
Click to view 3D structure	Procathepsin L	P25975	Bos taurus	Predicted (SEA)	Prediction Confidence Score 0.271 Applicability Domain 0.29 Low confidence Statistical Significance 0.0128 Supporting Reference Compounds 12 E-value 99.8027
Click to view 3D structure	Sodium-dependent noradrenaline transporter	P23975	Humans	Predicted (SEA)	Prediction Confidence Score 0.271 Applicability Domain 0.302 Statistical Significance 0.0806 Supporting Reference Compounds 451 E-value 627.776
Click to view 3D structure	Papain	P00784	Carica papaya	Predicted (SEA)	Prediction Confidence Score 0.27 Applicability Domain 0.29 Low confidence Statistical Significance 0.0227 Supporting Reference Compounds 35 E-value 176.406
Click to view 3D structure	Calpain-2 catalytic subunit	Q27971	Bos taurus	Predicted (SEA)	Prediction Confidence Score 0.269 Applicability Domain 0.269 Low confidence Statistical Significance 0.0176 Supporting Reference Compounds 1 E-value 137.326
Click to view 3D structure	Delta-type opioid receptor	P41143	Humans	Known	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.
Click to view 3D structure	Mu-type opioid receptor	P35372	Humans	Known	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.
Click to view 3D structure	Kappa-type opioid receptor	P41145	Humans	Known	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.

Concentrations

Not Available

External Links

DrugBank ID

DB06793

HMDB ID

Not Available

FooDB ID

Not Available

Phenol Explorer ID

Not Available

KNApSAcK ID

Not Available

BiGG ID

Not Available

BioCyc ID

Not Available

METLIN ID

Not Available

PDB ID

Not Available

Wikipedia Link

Levopropoxyphene

Chemspider ID

Not Available

ChEBI ID

51174

PubChem Compound ID

Not Available

Kegg Compound ID

Not Available

YMDB ID

Not Available

ECMDB ID

Not Available

References

Synthesis Reference

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

MSDS

Link

General References

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: 12818953]
Drugs.com - http://www.drugs.com/cons/Propoxyphene.html
RxList: The Internet Drug Index (2009). - http://www.rxlist.com/

Propoxyphene (CED0005127)

Structure for CHEM002237: Propoxyphene

Structure