Definition
Description
Top Gene Interactions
Related Pathways
General Information
- 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
- Uses/Sources: For the relief of mild to moderate pain
- Health Effects: Medical problems can include congested lungs, liver disease, tetanus, infection of the heart valves, skin abscesses, anemia and pneumonia. Death can occur from overdose.
- 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. (L1712)
- Route of Exposure: Oral
Toxicity
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: LD50: 230mg/kg (oral, rat)
Mechanism of Action
Target Name | Mechanism of Action | References |
---|---|---|
Mu-type opioid receptor Kappa-type opioid receptor Delta-type opioid receptor |
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. |
7562497 9399970 9783723 17159739 11752352 6249436 3559988 6258941 10690289 9020197 |
Dextropropoxyphene Interacts with Diseases
Disease | Inference Score | References/Inference Genes |
Cocaine dependence | 9.19 |
|
Orthostatic hypotension | 6.52 |
|
Epilepsy | 6.07 |
|
Drug dependence | 5.8 |
|
Epilepsy, Idiopathic Generalized | 5.05 |
|
Substance Withdrawal Syndrome | 5.03 |
|
Metabolism, Inborn Errors | 4.63 |
|
Morphine Dependence | 4.55 |
|
Heroin Dependence | 4.5 |
|
Opioid-Related Disorders | 4.44 | |
Seizures | 4.37 |
|
Hepatitis C | 4.25 |
|
Alcohol dependence | 4.11 |
|
Neuropathic pain | 4.01 |
|
Dyskinesias | 4.0 |
|
Kidney disease | 3.97 |
|
Hepatic Encephalopathy | 3.95 |
|
Constipation | 3.94 |
|
Amphetamine-Related Disorders | 3.81 | |
Hypercholesterolemia | 3.81 |
|