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 (0.39oz).[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]
↑アンビサ(2023-03-31)。「RDC No. 784 - Listas de Substâncias Entorpecentes、Psicotropicas、Precursoras e Outras sob Controle Especial」[大学理事会決議 No. 784 - 特別管理下の麻薬、向精神薬、前駆体、およびその他の物質のリスト] (ブラジルポルトガル語)。Diário Oficial da União (2023-04-04 公開)。2023-08-03 のオリジナルからアーカイブされました。2023-08-16に取得。
↑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. PMID11772223.
↑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. PMID8251291.
↑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. PMID7249503. S2CID10117158.
↑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. PMID2614458.
↑Appel WC (November 1987). "Possible roles of normeperidine and hyponatremia in a postoperative death". Canadian Medical Association Journal. 137 (10): 912–3. PMC1267380. PMID3676934.
↑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. PMID1585886. S2CID32005631.
↑ Ramírez J、Innocenti F、Schuetz EG、Flockhart DA、Relling MV、Santucci R、Ratain MJ (2004 年 9 月)。「CYP2B6、CYP3A4、および CYP2C19 は、ヒト肝ミクロソームにおけるメペリジンの in vitro N-脱メチル化に関与している」。Drug Metabolism and Disposition : The Biological Fate of Chemicals。32 (9): 930–6。doi : 10.1016 / S0090-9556( 24 ) 02975-1。PMID 15319333 。
↑ Frearson PM、Stern ES (1958)。「622 .ペチジンの新しい類似体。第III部。1-アリールオキシアルキルノルペチジン、および類似体」。Journal of the Chemical Society (Resumed) : 3065–7。doi : 10.1039 /JR9580003065。
↑ Frearson PM、Hardy DG、Stern ES (1960)。「426. ペチジンの新しい類似体。第 IV 部。環状エーテル基を含む 1 位の置換基」。Journal of the Chemical Society (Resumed) : 2103–7。doi : 10.1039 /JR9600002103。
