Specific binding of racemic oxazepam esters to rat brain synaptosomes and the influence of bioactivation by esterases.
Six aliphatic esters of oxazepam were investigated for 3H-diazepam displacing activity and hydrolysis in rat in the brain P2-fraction treated with diisopropylfluorophosphate. The esters are prodrugs in relation to oxazepam. Increasing size of the 3-substituent and steric hindrance increased the value of IC50. Controversial reports on oxazepam hemisuccinate could be explained by its stereoselective hydrolysis in vivo.
D000818:Animals; D001711:Biotransformation; D001921:Brain / Q000378:metabolism*; D003975:Diazepam / Q000378:metabolism; D004950:Esterases / Q000378:metabolism*; D004952:Esters; D066298:In Vitro Techniques; D007531:Isoflurophate / Q000494:pharmacology; D010076:Oxazepam / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D013237:Stereoisomerism; D013574:Synaptosomes / Q000378:metabolism*
D004952:Esters; D007531:Isoflurophate; D010076:Oxazepam; D004950:Esterases; D003975:Diazepam