2890 Propoxyphene Propoxyphene is only found in individuals that have used or taken this drug. It is 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]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. 469-62-5 25137868 C22H29NO2 339.219830 White powder. 75.5°C 3.32 mg/L (at 25°C) Oral 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. 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 LD50: 230mg/kg (oral, rat) No indication of carcinogenicity to humans (not listed by IARC). For the relief of mild to moderate pain Medical problems can include congested lungs, liver disease, tetanus, infection of the heart valves, skin abscesses, anemia and pneumonia. Death can occur from overdose. Coma, respiratory depression, circulatory collapse, and pulmonary edema. Seizures occur more frequently in patients with propoxyphene intoxication than in those with opiate intoxication. 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) 2009-07-21T20:27:20Z 2014-12-24T20:25:52Z Propoxyphene C07406 51173 Propoxyphene DB00647 true [H][C@](C)(CN(C)C)[C@@](CC1=CC=CC=C1)(OC(=O)CC)C1=CC=CC=C1 C22H29NO2 InChI=1/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+/s2 InChIKey=XLMALTXPSGQGBX-PEODTPIXNA-N 339.4712 339.219829177 Exogenous Solid 4.18 HMDB14785 21864756 <p>Carl R. White, &#8220;Synthesis and purification of d-propoxyphene hydrochloride.&#8221; U.S. Patent US4661625, issued April, 1973.</p>