Chemistry:Norpethidine

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Short description: Chemical compound
Norpethidine
Norpethidine2DACS.svg
Norpethidine 27feb.gif
Clinical data
Routes of
administration		N/A
ATC code
  • none
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC14H19NO2
Molar mass233.311 g·mol−1
3D model (JSmol)
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Norpethidine (normeperidine, pethidine intermediate B) is a 4-phenylpiperidine derivative that is both a precursor to, and the toxic metabolite of, pethidine (meperidine). It is scheduled by United Nations Single Convention on Narcotic Drugs. It is a Schedule II Narcotic controlled substance in the United States and has an ACSCN of 9233. The 2014 annual manufacturing quota was 11 grams (0.39 oz).[1]

Norpethidine is a controlled drug because of its potential uses in manufacturing both pethidine itself and a range of N-substituted derivatives, but it has little opioid activity in its own right. Instead, norpethidine acts as a stimulant and causes convulsions.[2][3]

Bioaccumulation of norpethidine is a major complication when pethidine is used in medicine as an analgesic, as when pethidine is used in high doses[4] or administered by intravenous infusion,[5] norpethidine can accumulate in the body at a faster rate than it is being excreted, particularly in elderly patients[6] or those with compromised liver or kidney function,[7] resulting in a range of toxic effects, mainly convulsions, but also myoclonus[8] and hyponatremia.[9] These complications can be serious and have sometimes resulted in death.[10]

Metabolism of pethidine to norpethidine is carried out mainly by the CYP enzymes, CYP2B6, CYP2C19 and CYP3A4, in the liver, and since the activity of these enzymes can vary between individuals and can be influenced by concurrent use of other drugs, the rate and extent of norpethidine production can be difficult to predict.[11][12]

Norpethidine can be used as a precursor in synthesis of other drugs, including etoxeridine,[13] benzethidine,[14] furethidine,[15] morpheridine, anileridine, phenoperidine, piminodine and oxpheneridine.

See also

References

  1. ↑ "Conversion Factors for Controlled Substances". Diversion Control Division. Drug Enforcement Administration (DEA), U.S. Department of Justice. http://www.deadiversion.usdoj.gov/quotas/conv_factor/index.html. 
  2. ↑ "Antinociceptive activity and toxicity of meperidine and normeperidine in mice". The Journal of Pharmacology and Experimental Therapeutics 223 (1): 203–6. October 1982. PMID 7120119. https://jpet.aspetjournals.org/content/223/1/203.short. 
  3. ↑ "Behavioural effects of norpethidine, a metabolite of pethidine, in rats". Toxicology 95 (1–3): 37–44. January 1995. doi:10.1016/0300-483x(94)02871-q. PMID 7825188. 
  4. ↑ "Use of meperidine in patient-controlled analgesia and the development of a normeperidine toxic reaction". Archives of Surgery (Chicago, Ill.) 137 (1): 84–8. January 2002. doi:10.1001/archsurg.137.1.84. PMID 11772223. 
  5. ↑ "Norpethidine toxicity and patient controlled analgesia". British Journal of Anaesthesia 71 (5): 738–40. November 1993. doi:10.1093/bja/71.5.738. PMID 8251291. 
  6. ↑ Holmberg L, Odar-Cederlof I, Boreus LO, Heyner L, Ehrnebo M. Comparative disposition of pethidine and norpethidine in old and young patients. European Journal of Clinical Pharmacology. 1982;22(2):175-9.
  7. ↑ "Presystemic metabolism of meperidine to normeperidine in normal and cirrhotic subjects". Clinical Pharmacology and Therapeutics 30 (2): 183–8. August 1981. doi:10.1038/clpt.1981.146. PMID 7249503. 
  8. ↑ "Norpethidine induced myoclonus in a patient with renal failure". Journal of Neurology, Neurosurgery, and Psychiatry 52 (12): 1450–1. December 1989. doi:10.1136/jnnp.52.12.1450. PMID 2614458. 
  9. ↑ "Possible roles of normeperidine and hyponatremia in a postoperative death". Canadian Medical Association Journal 137 (10): 912–3. November 1987. PMID 3676934. 
  10. ↑ "Lethal effects of normeperidine". The American Journal of Forensic Medicine and Pathology 13 (1): 42–3. March 1992. doi:10.1097/00000433-199203000-00009. PMID 1585886. 
  11. ↑ "CYP2B6, CYP3A4, and CYP2C19 are responsible for the in vitro N-demethylation of meperidine in human liver microsomes". Drug Metabolism and Disposition: The Biological Fate of Chemicals 32 (9): 930–6. September 2004. PMID 15319333. 
  12. ↑ "Norpethidine accumulation and generalized seizure during pethidine patient-controlled analgesia". Anaesthesia and Intensive Care 27 (3): 289–91. June 1999. PMID 10389564. 
  13. ↑ Henri M, "New piperidine derivatives", US patent granted 2858316, published 28 October 1958, assigned to UCB SA
  14. ↑ "622. Some new analogues of pethidine. Part III. 1-Aryloxy-alkylnorpethidines, and close analogues.". Journal of the Chemical Society (Resumed): 3065–7. 1958. doi:10.1039/JR9580003065. 
  15. ↑ "426. Some new analogues of pethidine. Part IV. Substituents at the 1-position incorporating cyclic ether groups.". Journal of the Chemical Society (Resumed): 2103–7. 1960. doi:10.1039/JR9600002103. 



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