title: 11C-labelling of the analgesic tramadol and its major metabolites by selective O- and N-methylation.
abstract: For in vivo pharmacokinetic studies with PET, the analgesic Tramadol(1-(3-methoxyphenyl)-2-dimethylaminomethyl-cyclohexan-1-ol ) and its major O- and N-desmethylated metabolites M1 and M2 were labelled with carbon-11. Starting with the corresponding desmethyl precursors, (1R,2R)-(+), (1S,2S)-(-)-[O-methyl-11C]Tramadol and racemic-[N-methyl-11C]Tramadol were prepared by methylation with n.c.a. [11C]methyl iodide in DMSO with radiochemical yields of 85 and 90%, respectively. Specific n.c.a. N-methylation of bis-desmethyl-Tramadol (M5) was achieved without base obtaining 11C-labelled (1R,2R)-(+)- and (1S,2S)-(-)-M1 with 90% radiochemical yield. However, a selective O-methylation of (+)- and (-)-M5 was not possible even with an excess of NaOH, and only 70% of (1R,2R)-(+)- and (1S,2S)-(-)-[O-methyl-11C]M2 was obtained. Quaternization of Tramadol or M1 was greater than 15 times slower than O-methylation, and was only observed in the presence of added CH3I carrier.
authors.affiliation: Institute für Nuklearchemie, Forschungszentrum Jülich GmbH, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Gail
authors.forename: H H
authors.initials: HH
authors.lastname: Coenen
authors.forename: K
authors.initials: K
authors.lastname: Hamacher
authors.forename: G
authors.initials: G
authors.lastname: Stöcklin
mesh_terms: D002250:Carbon Radioisotopes; D006801:Humans; D007553:Isotope Labeling / Q000379:methods*; D008745:Methylation; D014055:Tomography, Emission-Computed; D014147:Tramadol / Q000493:pharmacokinetics
chemical_list: D002250:Carbon Radioisotopes; D014147:Tramadol