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Norpethidine (Normeperidine, Pethidine Intermediate B) is a 4-phenylpiperidine derivative that is both a metabolite of and a precursor to pethidine (meperidine). It is scheduled by UN Single Convention on Narcotic Drugs. 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.〔Umans JG, Inturrisi CE. Antinociceptive activity and toxicity of meperidine and normeperidine in mice. ''Journal of Pharmacology and Experimental Therapeutics''. 1982 Oct;223(1):203-6.〕〔Plummer JL, Gourlay GK, Cmielewski PL, Odontiadis J, Harvey I. Behavioural effects of norpethidine, a metabolite of pethidine, in rats. ''Toxicology''. 1995 Jan 6;95(1-3):37-44.〕 Build up of norpethidine is a major complication when pethidine is used in medicine as an analgesic, as when pethidine is used in high doses〔Simopoulos TT, Smith HS, Peeters-Asdourian C, Stevens DS. Use of meperidine in patient-controlled analgesia and the development of a normeperidine toxic reaction. ''Archives of Surgery''. 2002 Jan;137(1):84-8.〕 or administered by intravenous infusion,〔Stone PA, Macintyre PE, Jarvis DA. Norpethidine toxicity and patient controlled analgesia. ''British Journal of Anaesthesia''. 1993 Nov;71(5):738-40.〕 norpethidine can accumulate in the body at a faster rate than it is being excreted, particularly in elderly patients〔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.〕 or those with compromised liver or kidney function,〔Pond SM, Tong T, Benowitz NL, Jacob P, Rigod J. Presystemic metabolism of meperidine to normeperidine in normal and cirrhotic subjects. ''Clinical Pharmacology and Therapeutics''. 1981 Aug;30(2):183-8.〕 resulting in a range of toxic effects, mainly convulsions, but also myoclonus〔Reutens DC, Stewart-Wynne EG. Norpethidine induced myoclonus in a patient with renal failure. ''Journal of Neurolology, Neurosurgery, and Psychiatry''. 1989 Dec;52(12):1450-1.〕 and hyponatremia.〔Appel WC. Possible roles of normeperidine and hyponatremia in a postoperative death. ''Canadian Medical Association Journal''. 1987 Nov 15;137(10):912-3.〕 These complications can be serious and have sometimes resulted in death.〔Jiraki K. Lethal effects of normeperidine. ''American Journal of Forensic Medicine and Pathology''. 1992 Mar;13(1):42-3.〕 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.〔Ramirez J, Innocenti F, Schuetz EG, Flockhart DA, Relling MV, Santucci R, Ratain MJ. CYP2B6, CYP3A4, and CYP2C19 are responsible for the in vitro N-demethylation of meperidine in human liver microsomes. ''Drug Metabolism and Disposition''. 2004 Sep;32(9):930-6.〕〔McHugh GJ. Norpethidine accumulation and generalized seizure during pethidine patient-controlled analgesia. ''Anaesthesia and Intensive Care''. 1999 Jun;27(3):289-91.〕 ==See also== * Nortilidine * O-Desmethyltramadol * Moramide intermediate * Methadone intermediate * Pethidine intermediate A * Pethidine intermediate C (pethidinic acid) 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Norpethidine」の詳細全文を読む スポンサード リンク
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