Norpethidine

Norpethidine

Systematic (IUPAC) name
ethyl 4-phenylpiperidine-4-carboxylate
Clinical data
Pregnancy cat.	?
Legal status	?
Routes	N/A
Identifiers
CAS number	77-17-8
ATC code	None
PubChem	CID 32414
ChemSpider	30039 Y
ChEMBL	CHEMBL1052 Y
Chemical data
Formula	C14H19NO2
Mol. mass	233.31 g/mol
SMILES	eMolecules & PubChem
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 Y Key:QKHMFBKXTNQCTM-UHFFFAOYSA-N Y
Y(what is this?)  (verify)

Norpethidine (Normeperidine, Pethidine Intermediate B) is a 4-phenylpiperidine derivative that is both a metabolite of and a precursor to pethidine (meperidine).

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.^[1][2]

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^[3] or administered by intravenous infusion,^[4] norpethidine can accumulate in the body at a faster rate than it is being excreted, particularly in elderly patients^[5] or those with compromised liver or kidney function,^[6] resulting in a range of toxic effects, mainly convulsions, but also myoclonus^[7] and hyponatremia.^[8] These complications can be serious and have sometimes resulted in death.^[9]

Metabolism of pethidine to norpethidine is carried out mainly by CYP enzymes in the liver, and since the activity of these enzymes can vary between individuals, the rate and extent of norpethidine production can be difficult to predict.^[10][11]

References

1. ^ 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.
2. ^ 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.
3. ^ 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.
4. ^ Stone PA, Macintyre PE, Jarvis DA. Norpethidine toxicity and patient controlled analgesia. British Journal of Anaesthesia. 1993 Nov;71(5):738-40.
5. ^ 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.
6. ^ 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.
7. ^ 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.
8. ^ Appel WC. Possible roles of normeperidine and hyponatremia in a postoperative death. Canadian Medical Association Journal. 1987 Nov 15;137(10):912-3.
9. ^ Jiraki K. Lethal effects of normeperidine. American Journal of Forensic Medicine and Pathology. 1992 Mar;13(1):42-3.
10. ^ 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.
11. ^ McHugh GJ. Norpethidine accumulation and generalized seizure during pethidine patient-controlled analgesia. Anaesthesia and Intensive Care. 1999 Jun;27(3):289-91.