[In vitro investigations of phase I metabolism of the fomocaine derivative Oe 9000 with pig liver homogenates].
2,2'-[4-(4-Phenoxymethylphenyl)butylimino]diethanol (Oe 9000) is a new, highly potent local anaesthetic related to fomocaine. It displays a long duration of action, low toxicity and is superior to fomocaine with regard to aqueous solubility and efficacy. In view of the development of new application forms, e.g. for the treatment of postoperative pain, the elucidation of the biotransformation of the drug is required. Therefore, experiments with 10000 x g supernatants and microsomes from pig liver homogenates were conducted. Using specifically synthesized reference compounds six phase I metabolites could be identified by LC-MS. Apart from the predominating oxidative desamination of the compound, that led after redox reactions to the corresponding butyric acid and butanol derivatives, oxygenation of the exocycle, oxidative N-desalkylation, and N-oxidation were observed. Thus, with the exception of one compound only metabolites are generated, that are expected to have no local anaesthetic activity due to their reduced basicity.
Dahse
T
T
Institut für Pharmazie, Friedrich-Schiller-Universität Jena, Germany. thomasdahse@web.de
Wennek-Klose
J
J
Listing
M
M
Fleck
C
C
Oelschläger
H
H
D000779:Anesthetics, Local / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D002849:Chromatography, Gas; D004983:Ethanolamines / Q000378:metabolism*; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008099:Liver / Q000378:metabolism*; D013058:Mass Spectrometry; D009569:Nitric Oxide / Q000737:chemistry; D010647:Phenyl Ethers / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D013552:Swine
C516051:2,2'-(4-(4-phenoxymethylphenyl)butylimino)diethanol; D000779:Anesthetics, Local; D004983:Ethanolamines; D007202:Indicators and Reagents; D010647:Phenyl Ethers; D009569:Nitric Oxide; C100275:fomocain