Drug/Small Molecule:

propoxyphene

Overview

Generic Names:	D-Propoxyphene; Dextropropoxyphene; Dextropropoxyphene-M; Dextroproxifeno; Propoxyphene HCl
IUPAC Name:	[4-dimethylamino-3-methyl-1,2-di(phenyl)butan-2-yl] propanoate
Trade 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
PharmGKB Accession Id:	PA451142

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]

Indication

For the relief of mild to moderate pain

ATC Therapeutic Category

• N02AC:Diphenylpropylamine derivatives

Pharmacology and Interactions

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.

Pharmacology

Propoxyphene, a synthetic opiate agonist, is structurally similar to methadone. 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.

Food Interactions

Take without regard to meals. Avoid alcohol.

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic

Half Life

6-12 hours

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)

Chemical Properties

Chemical Formula:

C₂₂H₂₉NO₂

SMILES Code:

CCC(=O)OC(Cc1ccccc1)(c2ccccc2)C(C)CN(C)C

(Format: OpenEye Isomeric)

Molecular Weight ( average / monoisotopic )

339.4712 / 339.2198

Curated Information

The following genes are in curated knowledge about this drug.

	Gene	Relationship	Evidence
	CYP2D6	CO    PK	Publications
	CYP3A	PK	Publications
	CYP3A4	PK	Publications
	CYP3A5	PK	Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other genes is available.

Metabolizing Enzymes

• CYP2D6

Drug Targets

• OPRM1
• OPRD1
• OPRK1

Curated Information

The following drugs are in curated knowledge about this drug.

	Drug	Relationship	Evidence
	warfarin		Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

acenocoumarol	Propoxyphene increases the anticoagulant effect
anisindione	Propoxyphene increases the anticoagulant effect
atomoxetine	The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
carbamazepine	Propoxyphene increases the effect of carbamazepine
cimetidine	Cimetidine increases the effect of the narcotic
dicumarol	Propoxyphene increases the anticoagulant effect
naltrexone	Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals
ritonavir	Ritonavir increases the levels of analgesic
warfarin	Propoxyphene increases the anticoagulant effect

Curated Information

The following diseases are in curated knowledge about this drug.

	Disease	Relationship	Evidence
	Bradycardia	CO    PK	Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

LinkOuts

Common Searches

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.