Identification of phenobarbital N-glucosides as urinary metabolites of phenobarbital in mice.
Previously, the N-glucosylation of phenobarbital had been observed only in humans. The results of a species screen (mouse, rat, guinea pig, rabbit, cat, dog, pig, and monkey) found that only mice excreted the N-glucosides of phenobarbital in urine after ip administration of sodium phenobarbital. The major diastereomer excreted by the mouse had the R configuration at the C-5 position of the barbiturate ring. The N-glucoside metabolites accounted for a small percentage of the dose (approximately 0.5%). Following ip dosing of the mouse with the phenobarbital N-glucosides, free phenobarbital could be detected in the urine. Upon ip or intercerebroventricular (icv) injection of the phenobarbital N-glucosides, minimal CNS activity was observed in the mouse.
Soine
W H
WH
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond 23298-0581.
Soine
P J
PJ
England
T M
TM
Ferkany
J W
JW
Agriesti
B E
BE
D000818:Animals; D000927:Anticonvulsants; D002415:Cats; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D010634:Phenobarbital / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology / Q000652:urine; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000187:drug effects; D013045:Species Specificity; D013552:Swine
D000927:Anticonvulsants; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; C017414:4-hydroxyphenobarbital; C043855:phenobarbital-N-glucoside; D010634:Phenobarbital