Identification and evaluation of O-alkyl substituted hydroxamic acids as potent in vitro inhibitors of the hepatic glycine cleavage system and investigation of their action on in vivo central nervous system glycine concentration.
The identification and evaluation of an extensive series of O-alkyl substituted hydroxamic acids as potent in vitro inhibitors of the hepatic glycine cleavage system is described. An investigation of the action of selected examples on the in vitro brain glycine cleavage system and their influence on in vivo plasma and central nervous system glycine concentrations following systemic administration is also reported.
Johnson
G
G
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Department of Chemistry, Ann Arbor, MI.
Boxer
P A
PA
Drummond
J T
JT
Boyd
D K
DK
Anderson
R J
RJ
D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism*; D005998:Glycine / Q000097:blood / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000032:analysis* / Q000493:pharmacokinetics / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013116:Spinal Cord / Q000378:metabolism
D006877:Hydroxamic Acids; D005998:Glycine