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 UNSingle 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).[2]
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.[3][4]
Bioaccumulation of norpethidine is a major complication when pethidine is used in medicine as an analgesic, as when pethidine is used in high doses[5] or administered by intravenous infusion,[6] norpethidine can accumulate in the body at a faster rate than it is being excreted, particularly in elderly patients[7] or those with compromised liver or kidney function,[8] resulting in a range of toxic effects, mainly convulsions, but also myoclonus[9] and hyponatremia.[10] These complications can be serious and have sometimes resulted in death.[11]
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.[12][13]
^Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). from the original on 2023-08-03. Retrieved 2023-08-16.
^"Conversion Factors for Controlled Substances". Diversion Control Division. Drug Enforcement Administration (DEA), U.S. Department of Justice.
^Umans JG, Inturrisi CE (October 1982). "Antinociceptive activity and toxicity of meperidine and normeperidine in mice". The Journal of Pharmacology and Experimental Therapeutics. 223 (1): 203–6. PMID 7120119.
^Plummer JL, Gourlay GK, Cmielewski PL, Odontiadis J, Harvey I (January 1995). "Behavioural effects of norpethidine, a metabolite of pethidine, in rats". Toxicology. 95 (1–3): 37–44. doi:10.1016/0300-483x(94)02871-q. PMID 7825188.
^Simopoulos TT, Smith HS, Peeters-Asdourian C, Stevens DS (January 2002). "Use of meperidine in patient-controlled analgesia and the development of a normeperidine toxic reaction". Archives of Surgery. 137 (1). Chicago, Ill.: 84–8. doi:10.1001/archsurg.137.1.84. PMID 11772223.
^Stone PA, Macintyre PE, Jarvis DA (November 1993). "Norpethidine toxicity and patient controlled analgesia". British Journal of Anaesthesia. 71 (5): 738–40. doi:10.1093/bja/71.5.738. PMID 8251291.
^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.
^Pond SM, Tong T, Benowitz NL, Jacob P, Rigod J (August 1981). "Presystemic metabolism of meperidine to normeperidine in normal and cirrhotic subjects". Clinical Pharmacology and Therapeutics. 30 (2): 183–8. doi:10.1038/clpt.1981.146. PMID 7249503. S2CID 10117158.
^Reutens DC, Stewart-Wynne EG (December 1989). "Norpethidine induced myoclonus in a patient with renal failure". Journal of Neurology, Neurosurgery, and Psychiatry. 52 (12): 1450–1. doi:10.1136/jnnp.52.12.1450. PMC1031622. PMID 2614458.
^Appel WC (November 1987). "Possible roles of normeperidine and hyponatremia in a postoperative death". Canadian Medical Association Journal. 137 (10): 912–3. PMC1267380. PMID 3676934.
^Jiraki K (March 1992). "Lethal effects of normeperidine". The American Journal of Forensic Medicine and Pathology. 13 (1): 42–3. doi:10.1097/00000433-199203000-00009. PMID 1585886. S2CID 32005631.
^Ramírez J, Innocenti F, Schuetz EG, Flockhart DA, Relling MV, Santucci R, Ratain MJ (September 2004). "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. PMID 15319333.
^McHugh GJ (June 1999). "Norpethidine accumulation and generalized seizure during pethidine patient-controlled analgesia". Anaesthesia and Intensive Care. 27 (3): 289–91. PMID 10389564.
^US granted 2858316, Henri M, "New piperidine derivatives", published 28 October 1958, assigned to UCB SA
^Frearson PM, Stern ES (1958). "622. Some new analogues of pethidine. Part III. 1-Aryloxy-alkylnorpethidines, and close analogues". Journal of the Chemical Society (Resumed): 3065–7. doi:10.1039/JR9580003065.
^Frearson PM, Hardy DG, Stern ES (1960). "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. doi:10.1039/JR9600002103.
January 01, 1970
norpethidine, normeperidine, pethidine, intermediate, phenylpiperidine, derivative, that, both, precursor, toxic, metabolite, pethidine, meperidine, scheduled, single, convention, narcotic, drugs, schedule, narcotic, controlled, substance, united, states, acsc. 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 UN 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 2 NorpethidineClinical dataAddictionliabilityHighRoutes ofadministrationN AATC codenoneLegal statusLegal statusAU Unscheduled BR Class A1 Narcotic drugs 1 CA Schedule I DE Anlage II Authorized trade only not prescriptible US Schedule II UN Narcotic Schedule IIdentifiersIUPAC name Ethyl 4 phenylpiperidine 4 carboxylateCAS Number77 17 8 YPubChem CID32414ChemSpider30039 YUNIIJG096PMW2NKEGGC22685ChEMBLChEMBL1052 YCompTox Dashboard EPA DTXSID50227806ECHA InfoCard100 000 918Chemical and physical dataFormulaC 14H 19N O 2Molar mass233 311 g mol 13D model JSmol Interactive imageSMILES O C OCC C2 c1ccccc1 CCNCC2InChI InChI 1S C14H19NO2 c1 2 17 13 16 14 8 10 15 11 9 14 12 6 4 3 5 7 12 h3 7 15H 2 8 11H2 1H3 YKey QKHMFBKXTNQCTM UHFFFAOYSA N Y verify 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 3 4 Bioaccumulation of norpethidine is a major complication when pethidine is used in medicine as an analgesic as when pethidine is used in high doses 5 or administered by intravenous infusion 6 norpethidine can accumulate in the body at a faster rate than it is being excreted particularly in elderly patients 7 or those with compromised liver or kidney function 8 resulting in a range of toxic effects mainly convulsions but also myoclonus 9 and hyponatremia 10 These complications can be serious and have sometimes resulted in death 11 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 12 13 Norpethidine can be used as a precursor in synthesis of other drugs including etoxeridine 14 benzethidine 15 furethidine 16 morpheridine anileridine phenoperidine piminodine and oxpheneridine See also editNortilidine O Desmethyltramadol Moramide intermediate Methadone intermediate Pethidine intermediate A Pethidine intermediate C pethidinic acid References edit Anvisa 2023 03 31 RDC Nº 784 Listas de Substancias Entorpecentes Psicotropicas Precursoras e Outras sob Controle Especial Collegiate Board Resolution No 784 Lists of Narcotic Psychotropic Precursor and Other Substances under Special Control in Brazilian Portuguese Diario Oficial da Uniao published 2023 04 04 Archived from the original on 2023 08 03 Retrieved 2023 08 16 Conversion Factors for Controlled Substances Diversion Control Division Drug Enforcement Administration DEA U S Department of Justice Umans JG Inturrisi CE October 1982 Antinociceptive activity and toxicity of meperidine and normeperidine in mice The Journal of Pharmacology and Experimental Therapeutics 223 1 203 6 PMID 7120119 Plummer JL Gourlay GK Cmielewski PL Odontiadis J Harvey I January 1995 Behavioural effects of norpethidine a metabolite of pethidine in rats Toxicology 95 1 3 37 44 doi 10 1016 0300 483x 94 02871 q PMID 7825188 Simopoulos TT Smith HS Peeters Asdourian C Stevens DS January 2002 Use of meperidine in patient controlled analgesia and the development of a normeperidine toxic reaction Archives of Surgery 137 1 Chicago Ill 84 8 doi 10 1001 archsurg 137 1 84 PMID 11772223 Stone PA Macintyre PE Jarvis DA November 1993 Norpethidine toxicity and patient controlled analgesia British Journal of Anaesthesia 71 5 738 40 doi 10 1093 bja 71 5 738 PMID 8251291 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 Pond SM Tong T Benowitz NL Jacob P Rigod J August 1981 Presystemic metabolism of meperidine to normeperidine in normal and cirrhotic subjects Clinical Pharmacology and Therapeutics 30 2 183 8 doi 10 1038 clpt 1981 146 PMID 7249503 S2CID 10117158 Reutens DC Stewart Wynne EG December 1989 Norpethidine induced myoclonus in a patient with renal failure Journal of Neurology Neurosurgery and Psychiatry 52 12 1450 1 doi 10 1136 jnnp 52 12 1450 PMC 1031622 PMID 2614458 Appel WC November 1987 Possible roles of normeperidine and hyponatremia in a postoperative death Canadian Medical Association Journal 137 10 912 3 PMC 1267380 PMID 3676934 Jiraki K March 1992 Lethal effects of normeperidine The American Journal of Forensic Medicine and Pathology 13 1 42 3 doi 10 1097 00000433 199203000 00009 PMID 1585886 S2CID 32005631 Ramirez J Innocenti F Schuetz EG Flockhart DA Relling MV Santucci R Ratain MJ September 2004 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 PMID 15319333 McHugh GJ June 1999 Norpethidine accumulation and generalized seizure during pethidine patient controlled analgesia Anaesthesia and Intensive Care 27 3 289 91 PMID 10389564 US granted 2858316 Henri M New piperidine derivatives published 28 October 1958 assigned to UCB SA Frearson PM Stern ES 1958 622 Some new analogues of pethidine Part III 1 Aryloxy alkylnorpethidines and close analogues Journal of the Chemical Society Resumed 3065 7 doi 10 1039 JR9580003065 Frearson PM Hardy DG Stern ES 1960 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 doi 10 1039 JR9600002103 Retrieved from https en wikipedia org w index php title Norpethidine amp oldid 1219869742, wikipedia, wiki, book, books, library,
