title: N-(trifluoromethyl)benzyl substituted N-normetazocines and N-norketobemidones.
abstract: To further investigate the unusual profile of N-benzyl substituted opioids, N-trifluoromethylbenzyl normetazocines and norketobemidones were prepared. The introduction of trifluoromethyl substituents on the benzyl group of the (-)-metazocines reduced affinity at all three receptors, with the greatest loss at kappa receptors. Surprisingly, some of the (+)-normetazocines actually possessed higher affinity than the corresponding (-)-isomers. In the ketobemidone series, the effects were different-the 4-trifluoromethyl substituted ketobemidone actually possessed 3-fold higher mu affinity than the unsubstituted parent to give a ligand with good mu affinity. In functional in vitro assays, this compound was a weak antagonists, but in apparent contradiction it was inactive in in vivo assays.
authors.affiliation: Department of Pharmacology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.
authors.forename: Everette L
authors.initials: EL
authors.lastname: May
authors.forename: Andrew
authors.initials: A
authors.lastname: Coop
authors.forename: James H
authors.initials: JH
authors.lastname: Woods
authors.forename: Mario D
authors.initials: MD
authors.lastname: Aceto
authors.forename: Edward R
authors.initials: ER
authors.lastname: Bowman
authors.forename: Louis S
authors.initials: LS
authors.lastname: Harris
authors.forename: John R
authors.initials: JR
authors.lastname: Traynor
mesh_terms: D000701:Analgesics, Opioid / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001392:Azocines / Q000737:chemistry* / Q000494:pharmacology; D001555:Benzene Derivatives / Q000737:chemistry* / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects; D010880:Piperidines / Q000737:chemistry* / Q000494:pharmacology; D011869:Radioligand Assay; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013460:Sulfur Isotopes
chemical_list: D000701:Analgesics, Opioid; D001392:Azocines; D001555:Benzene Derivatives; D010880:Piperidines; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013460:Sulfur Isotopes; D006160:Guanosine Triphosphate