Norpropoxyphene
Names
Preferred IUPAC name
(2S,3R)-3-Methyl-4-(methylamino)-1,2-diphenylbutan-2-yl propanoate
Identifiers
3D model (JSmol)
ChemSpider
UNII
  • InChI=1S/C21H27NO2/c1-4-20(23)24-21(17(2)16-22-3,19-13-9-6-10-14-19)15-18-11-7-5-8-12-18/h5-14,17,22H,4,15-16H2,1-3H3/t17-,21+/m1/s1 checkY
    Key: IKACRWYHQXOSGM-UTKZUKDTSA-N checkY
  • InChI=1/C21H27NO2/c1-4-20(23)24-21(17(2)16-22-3,19-13-9-6-10-14-19)15-18-11-7-5-8-12-18/h5-14,17,22H,4,15-16H2,1-3H3/t17-,21+/m1/s1
    Key: IKACRWYHQXOSGM-UTKZUKDTBF
  • O=C(O[C@@](c1ccccc1)(Cc2ccccc2)[C@H](C)CNC)CC
Properties
C21H27NO2
Molar mass 325.445
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Norpropoxyphene is a major metabolite of the opioid analgesic drug dextropropoxyphene,[1] and is responsible for many of the side effects associated with use of this drug, especially the unusual toxicity seen during dextropropoxyphene overdose.[2][3][4] It has weaker analgesic effects than dextropropoxyphene itself, but is a relatively potent pro-convulsant and blocker of sodium and potassium channels,[5] particularly in heart tissue,[6][7] which produces prolonged intracardiac conduction time and can lead to heart failure following even relatively minor overdoses.[8][9][10][11] The toxicity of this metabolite makes dextropropoxyphene up to 10 times more likely to cause death following overdose compared to other similar mild opioid analgesics,[12] and has led to dextropropoxyphene being withdrawn from the market in some countries.[13]

Because norpropoxyphene has a long half-life in the body of up to 36 hours (compared to around 6–12 hours for dextropropoxyphene), it can accumulate in tissues during chronic use of dextropropoxyphene-containing medications, especially in people whose excretion of drugs is slower than normal such as young children, the elderly, and individuals with reduced kidney or liver function, and so side effects including serious adverse events are more common in these groups and use of dextropropoxyphene should be avoided where possible.[14][15][16]

References

  1. ↑ Somogyi AA, Menelaou A, Fullston SV (October 2004). "CYP3A4 mediates dextropropoxyphene N-demethylation to nordextropropoxyphene: human in vitro and in vivo studies and lack of CYP2D6 involvement". Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 34 (10): 875–87. doi:10.1080/00498250400008371. PMID 15764408. S2CID 7680532.
  2. ↑ Gustafson A, Gustafsson B (1976). "Acute poisoning with dextropropoxyphene. Clinical symptoms and plasma concentrations". Acta Medica Scandinavica. 200 (4): 241–8. doi:10.1111/j.0954-6820.1976.tb08226.x. PMID 983792.
  3. ↑ McBay AJ (August 1976). "Propoxyphene and norpropoxyphene concentrations in blood and tissues in cases of fatal overdose". Clinical Chemistry. 22 (8): 1319–21. doi:10.1093/clinchem/22.8.1319. PMID 949842.
  4. ↑ Nickander RC, Emmerson JL, Hynes MD, Steinberg MI, Sullivan HR (August 1984). "Pharmacologic and toxic effects in animals of dextropropoxyphene and its major metabolite norpropoxyphene: a review". Human Toxicology. 3 Suppl: 13S–36S. doi:10.1177/096032718400300103. PMID 6090306. S2CID 1333582.
  5. ↑ Nickander R, Smits SE, Steinberg MI (January 1977). "Propoxyphene and norpropoxyphene: pharmacologic and toxic effects in animals". The Journal of Pharmacology and Experimental Therapeutics. 200 (1): 245–53. PMID 13200.
  6. ↑ Lund-Jacobsen H (March 1978). "Cardio-respiratory toxicity of propoxyphene and norpropoxyphene in conscious rabbits". Acta Pharmacologica et Toxicologica. 42 (3): 171–8. doi:10.1111/j.1600-0773.1978.tb02187.x. PMID 580345.
  7. ↑ Ulens C, Daenens P, Tytgat J (December 1999). "Norpropoxyphene-induced cardiotoxicity is associated with changes in ion-selectivity and gating of HERG currents". Cardiovascular Research. 44 (3): 568–78. doi:10.1016/s0008-6363(99)00258-8. PMID 10690289.
  8. ↑ Young RJ (July 1983). "Dextropropoxyphene overdosage. Pharmacological considerations and clinical management". Drugs. 26 (1): 70–9. doi:10.2165/00003495-198326010-00004. PMID 6349964. S2CID 46978533.
  9. ↑ Lawson AA, Northridge DB (1987). "Dextropropoxyphene overdose. Epidemiology, clinical presentation and management". Medical Toxicology and Adverse Drug Experience. 2 (6): 430–44. doi:10.1007/BF03259877. PMID 3323775. S2CID 13452948.
  10. ↑ Afshari R, Maxwell S, Dawson A, Bateman DN (2005). "ECG abnormalities in co-proxamol (paracetamol/dextropropoxyphene) poisoning". Clinical Toxicology. 43 (4): 255–9. doi:10.1081/CLT-66069. PMID 16035201. S2CID 36817890.
  11. ↑ Simkin S, Hawton K, Sutton L, Gunnell D, Bennewith O, Kapur N (March 2005). "Co-proxamol and suicide: preventing the continuing toll of overdose deaths". QJM. 98 (3): 159–70. doi:10.1093/qjmed/hci026. PMID 15728397.
  12. ↑ Afshari R, Good AM, Maxwell SR, Bateman DN (October 2005). "Co-proxamol overdose is associated with a 10-fold excess mortality compared with other paracetamol combination analgesics". British Journal of Clinical Pharmacology. 60 (4): 444–7. doi:10.1111/j.1365-2125.2005.02468.x. PMC 1884826. PMID 16187978.
  13. ↑ Sandilands EA, Bateman DN (August 2008). "Co-proxamol withdrawal has reduced suicide from drugs in Scotland". British Journal of Clinical Pharmacology. 66 (2): 290–3. doi:10.1111/j.1365-2125.2008.03206.x. PMC 2492929. PMID 18489609.
  14. ↑ Gibson TP, Giacomini KM, Briggs WA, Whitman W, Levy G (May 1980). "Propoxyphene and norpropoxyphene plasma concentrations in the anephric patient". Clinical Pharmacology and Therapeutics. 27 (5): 665–70. doi:10.1038/clpt.1980.94. PMID 7371364. S2CID 24099122.
  15. ↑ Inturrisi CE, Colburn WA, Verebey K, Dayton HE, Woody GE, O'Brien CP (February 1982). "Propoxyphene and norpropoxyphene kinetics after single and repeated doses of propoxyphene". Clinical Pharmacology and Therapeutics. 31 (2): 157–67. doi:10.1038/clpt.1982.25. PMID 7056023. S2CID 38421623.
  16. ↑ Flanagan RJ, Johnston A, White AS, Crome P (October 1989). "Pharmacokinetics of dextropropoxyphene and nordextropropoxyphene in young and elderly volunteers after single and multiple dextropropoxyphene dosage". British Journal of Clinical Pharmacology. 28 (4): 463–9. doi:10.1111/j.1365-2125.1989.tb03527.x. PMC 1379997. PMID 2590604.
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