title: A new placental enzyme in the metabolism of cocaine: an in vitro animal model.
abstract: OBJECTIVE
  The aim of this study was to analyze placental metabolism in a genetically controlled in vitro animal model.
  
  
  METHODS
  Placentas from Sprague-Dawley rats were centrifuged, and microsomes were isolated. Four treatment groups were incubated with cocaine over four time periods: placental microsomes + cocaine, placental microsomes + diisopropyl fluorophosphate (an anticholinesterase) + cocaine, placental microsomes + cocaine + butyrylcholinesterase, and a blank (cocaine only). Gas chromatography was used to quantify cocaine (Limit of quantitation = 19 ng/ml) and metabolites. Gas chromatography/mass spectrometry was used to verify the identity of the metabolites.
  
  
  RESULTS
  Butyrylcholinesterase enhanced cocaine metabolism to ecgonine methyl ester. More than 40% of cocaine was metabolized to norcocaine by rat placental when diisopropyl fluorophosphate suppressed cocaine. Norcocaine is produced by hepatic N-demethylase action on methyl-bearing nitrogen in cocaine, suggesting that placenta and liver have this capacity. Gas chromatography/mass spectrometry was essential to the identification of norcocaine, because norcocaine is frequently not identified.
  
  
  CONCLUSIONS
  This biotransformation of cocaine to norcocaine may be a primary metabolic pathway induced in the cholinesterase-deficient placenta. This has clinical implications because norcocaine is ninefold more active physiologically than cocaine or ecgononine methylesterase.
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas 75235-9032, USA.
authors.forename: B B
authors.initials: BB
authors.lastname: Little
authors.forename: D A
authors.initials: DA
authors.lastname: Roe
authors.forename: R W
authors.initials: RW
authors.lastname: Stettler
authors.forename: V R
authors.initials: VR
authors.lastname: Bohman
authors.forename: K L
authors.initials: KL
authors.lastname: Westfall
authors.forename: S
authors.initials: S
authors.lastname: Sobhi
mesh_terms: D000818:Animals; D001711:Biotransformation; D002091:Butyrylcholinesterase / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000493:pharmacokinetics; D005260:Female; D007531:Isoflurophate / Q000494:pharmacology; D008861:Microsomes / Q000201:enzymology / Q000378:metabolism; D008954:Models, Biological; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D010920:Placenta / Q000201:enzymology* / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007531:Isoflurophate; C008671:norcocaine; D010089:Oxidoreductases, N-Demethylating; D002091:Butyrylcholinesterase; D003042:Cocaine; C034524:ecgonine methyl ester