去甲哌替啶

**去甲哌替啶**
臨床資料
给药途径	N/A
ATC碼	未分配;
法律規範狀態
法律規範	澳：未列入管制; 加：Schedule I; 德：Anlage II; 美：附表II; UN：Narcotic Schedule I;
识别信息
	IUPAC命名法 Ethyl 4-phenylpiperidine-4-carboxylate; ;
CAS号	77-17-8
PubChem CID	32414;
ChemSpider	30039 ;
UNII	JG096PMW2N;
KEGG	C22685;
ChEMBL	ChEMBL1052 ;
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID50227806 ;
ECHA InfoCard	100.000.918
化学信息
化学式	C14H19NO2
摩尔质量	233.31 g·mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES O=C(OCC)C2(c1ccccc1)CCNCC2;
	InChI 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 ; Key:QKHMFBKXTNQCTM-UHFFFAOYSA-N ;

去甲哌替啶是一种4-苯基哌啶的衍生物，化学式为C₁₄H₁₉NO₂。它是哌替啶的前体及有毒代谢物。它被列入联合国麻醉品单一公约，也被美国列入到受管制物质法案附表II，2014年的生产限额为11克（0.39盎司）。^[1]

去甲哌替啶因可用于合成哌替啶及相关的N-取代衍生物（如依托利定（英语：etoxeridine）^[2]、苄替啶（英语：benzethidine）^[3]、呋替啶（英语：furethidine）^[4]）而受到管制。不过，去甲哌替啶本身的类阿片作用低，是一种引起抽搐的兴奋剂。^[5]^[6]

当把哌替啶用作镇痛药时，就要大剂量使用^[7]或静脉注射哌替啶。^[8]这会去甲哌替啶产生的速率比排泄去甲哌替啶的速率快，导致去甲哌替啶累积产生的并发症，包括抽搐、肌阵挛^[9]、低血钠症。^[10]这些并发症可能会很严重，甚至可能导致死亡。^[11]这些并发症在老年人^[12]及肝功能或肾功能受损的人^[13]身上更明显。

哌替啶在体内会被肝脏属于细胞色素P450的CYP2B6、CYP2C19、CYP3A4代谢成去甲哌替啶。由于这些酶的活性因人而异，且可能受到共服的其它药物影响，因此很难预测产生去甲哌替啶的速率。^[14]^[15]

参考资料[编辑]

^ Conversion Factors for Controlled Substances. Diversion Control Division. Drug Enforcement Administration (DEA), U.S. Department of Justice.
^ US granted 2858316,Henri M,「New piperidine derivatives」,发表于28 October 1958,指定于UCB SA
^ Frearson PM, Stern ES. 622. Some new analogues of pethidine. Part III. 1-Aryloxy-alkylnorpethidines, and close analogues.. Journal of the Chemical Society (Resumed). 1958: 3065–7. doi:10.1039/JR9580003065.
^ Frearson PM, Hardy DG, Stern ES. 426. Some new analogues of pethidine. Part IV. Substituents at the 1-position incorporating cyclic ether groups.. Journal of the Chemical Society (Resumed). 1960: 2103–7. doi:10.1039/JR9600002103.
^ Umans JG, Inturrisi CE. Antinociceptive activity and toxicity of meperidine and normeperidine in mice. The Journal of Pharmacology and Experimental Therapeutics. October 1982, 223 (1): 203–6. PMID 7120119.
^ Plummer JL, Gourlay GK, Cmielewski PL, Odontiadis J, Harvey I. Behavioural effects of norpethidine, a metabolite of pethidine, in rats. Toxicology. January 1995, 95 (1–3): 37–44. PMID 7825188. doi:10.1016/0300-483x(94)02871-q.
^ 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 (Chicago, Ill.). January 2002, 137 (1): 84–8. PMID 11772223. doi:10.1001/archsurg.137.1.84 .
^ Stone PA, Macintyre PE, Jarvis DA. Norpethidine toxicity and patient controlled analgesia. British Journal of Anaesthesia. November 1993, 71 (5): 738–40. PMID 8251291. doi:10.1093/bja/71.5.738 .
^ Reutens DC, Stewart-Wynne EG. Norpethidine induced myoclonus in a patient with renal failure. Journal of Neurology, Neurosurgery, and Psychiatry. December 1989, 52 (12): 1450–1. PMC 1031622 . PMID 2614458. doi:10.1136/jnnp.52.12.1450.
^ Appel WC. Possible roles of normeperidine and hyponatremia in a postoperative death. Canadian Medical Association Journal. November 1987, 137 (10): 912–3. PMC 1267380 . PMID 3676934.
^ Jiraki K. Lethal effects of normeperidine. The American Journal of Forensic Medicine and Pathology. March 1992, 13 (1): 42–3. PMID 1585886. S2CID 32005631. doi:10.1097/00000433-199203000-00009.
^ Holmberg, L.; Odar-Cederlöf, I.; Boréus, L. O.; Heyner, L.; Ehrnebo, M. Comparative disposition of pethidine and norpethidine in old and young patients. European Journal of Clinical Pharmacology. 1982, 22 (2): 175–179. ISSN 0031-6970. doi:10.1007/BF00542464.
^ 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. August 1981, 30 (2): 183–8. PMID 7249503. S2CID 10117158. doi:10.1038/clpt.1981.146.
^ Ramírez 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: The Biological Fate of Chemicals. September 2004, 32 (9): 930–6. PMID 15319333.
^ McHugh GJ. Norpethidine accumulation and generalized seizure during pethidine patient-controlled analgesia. Anaesthesia and Intensive Care. June 1999, 27 (3): 289–91. PMID 10389564.

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[1] Conversion Factors for Controlled Substances. Diversion Control Division. Drug Enforcement Administration (DEA), U.S. Department of Justice.

[2] US granted 2858316,Henri M,「New piperidine derivatives」,发表于28 October 1958,指定于UCB SA

[3] Frearson PM, Stern ES. 622. Some new analogues of pethidine. Part III. 1-Aryloxy-alkylnorpethidines, and close analogues.. Journal of the Chemical Society (Resumed). 1958: 3065–7. doi:10.1039/JR9580003065.

[4] Frearson PM, Hardy DG, Stern ES. 426. Some new analogues of pethidine. Part IV. Substituents at the 1-position incorporating cyclic ether groups.. Journal of the Chemical Society (Resumed). 1960: 2103–7. doi:10.1039/JR9600002103.

[pmid7120119-5] Umans JG, Inturrisi CE. Antinociceptive activity and toxicity of meperidine and normeperidine in mice. The Journal of Pharmacology and Experimental Therapeutics. October 1982, 223 (1): 203–6. PMID 7120119.

[pmid7825188-6] Plummer JL, Gourlay GK, Cmielewski PL, Odontiadis J, Harvey I. Behavioural effects of norpethidine, a metabolite of pethidine, in rats. Toxicology. January 1995, 95 (1–3): 37–44. PMID 7825188. doi:10.1016/0300-483x(94)02871-q.

[pmid11772223-7] 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 (Chicago, Ill.). January 2002, 137 (1): 84–8. PMID 11772223. doi:10.1001/archsurg.137.1.84 .

[pmid8251291-8] Stone PA, Macintyre PE, Jarvis DA. Norpethidine toxicity and patient controlled analgesia. British Journal of Anaesthesia. November 1993, 71 (5): 738–40. PMID 8251291. doi:10.1093/bja/71.5.738 .

[pmid2614458-9] Reutens DC, Stewart-Wynne EG. Norpethidine induced myoclonus in a patient with renal failure. Journal of Neurology, Neurosurgery, and Psychiatry. December 1989, 52 (12): 1450–1. PMC 1031622 . PMID 2614458. doi:10.1136/jnnp.52.12.1450.

[pmid3676934-10] Appel WC. Possible roles of normeperidine and hyponatremia in a postoperative death. Canadian Medical Association Journal. November 1987, 137 (10): 912–3. PMC 1267380 . PMID 3676934.

[pmid1585886-11] Jiraki K. Lethal effects of normeperidine. The American Journal of Forensic Medicine and Pathology. March 1992, 13 (1): 42–3. PMID 1585886. S2CID 32005631. doi:10.1097/00000433-199203000-00009.

[12] Holmberg, L.; Odar-Cederlöf, I.; Boréus, L. O.; Heyner, L.; Ehrnebo, M. Comparative disposition of pethidine and norpethidine in old and young patients. European Journal of Clinical Pharmacology. 1982, 22 (2): 175–179. ISSN 0031-6970. doi:10.1007/BF00542464.

[pmid7249503-13] 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. August 1981, 30 (2): 183–8. PMID 7249503. S2CID 10117158. doi:10.1038/clpt.1981.146.

[pmid15319333-14] Ramírez 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: The Biological Fate of Chemicals. September 2004, 32 (9): 930–6. PMID 15319333.

[pmid10389564-15] McHugh GJ. Norpethidine accumulation and generalized seizure during pethidine patient-controlled analgesia. Anaesthesia and Intensive Care. June 1999, 27 (3): 289–91. PMID 10389564.

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