Stereoselective binding of 3-acetoxy-, and 3-hydroxy-1,4-benzodiazepine-2-ones to human serum albumin. Selective allosteric interaction with warfarin enantiomers.
Stereoselective binding of oxazepam, lorazepam, temazepam and methyl lorazepam as well as of their acetates to human serum albumin was investigated by different techniques. The 2'-chlorine and the N(1)-methyl substitution exert opposite effects on the antipodes. Enantiomers of oxazepam acetate (OAc) and lorazepam acetate (LAc) displace diazepam. Allosteric interactions with warfarin were manifested by either mutually increased or decreased binding depending on the structure of benzodiazepine and on the configuration of both benzodiazepine and warfarin. The most remarkable effect could be observed in the simultaneous binding of (S)-lorazepam acetate and (S)-warfarin.
D001569:Benzodiazepines / Q000378:metabolism*; D003975:Diazepam / Q000378:metabolism; D006801:Humans; D008140:Lorazepam / Q000031:analogs & derivatives / Q000378:metabolism; D010076:Oxazepam / Q000031:analogs & derivatives / Q000378:metabolism; D012107:Research Design; D012709:Serum Albumin / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014462:Ultrafiltration; D014859:Warfarin / Q000378:metabolism
D012709:Serum Albumin; D001569:Benzodiazepines; D014859:Warfarin; C028246:oxazepam acetate; D010076:Oxazepam; D008140:Lorazepam; D003975:Diazepam; C028245:lorazepam acetate