Biotransformation of N-methylcyclobarbital in vivo in rabbit and rat.
Metabolism of N-methylcyclobarbital in the rabbit and rat has been studied in vivo for the purpose of comparison with the C5-methylated analogue, hexobarbital. In the rabbit, the main route of the metabolism of N-methylcyclobarbital is glucuronide formation after hydroxylation at the 3'-position of the parent compound. Dehydrogenation of the 3'-hydroxy product, a major pathway in the metabolism of hexobarbital, was a minor route in the case of N-methylcyclobarbital. In addition, a new type of metabolite, thought to be dihydroxylated products from spectral studies, was isolated. In the rat, there were almost no differences in the metabolic fates of N-methylcyclobarbital and hexobarbital. Profiles of metabolism of four analogous barbiturates (N-methylcyclobarbital, hexobarbital, cyclobarbital and norhexobarbital), which have a cyclohexene ring on the 5-carbon, reveal the contribution of alkyl substituents in the barbiturate ring on the bioavailability and metabolism of these compounds.
Miyano
K
K
Shimodouzono
Y
Y
Toki
S
S
D000818:Animals; D001463:Barbiturates / Q000031:analogs & derivatives / Q000378:metabolism*; D001711:Biotransformation; D005965:Glucuronates / Q000096:biosynthesis; D006591:Hexobarbital / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008968:Molecular Conformation; D011817:Rabbits / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains / Q000378:metabolism*; D012890:Sleep; D013045:Species Specificity; D013329:Structure-Activity Relationship; D014556:Urine / Q000032:analysis
D001463:Barbiturates; D005965:Glucuronates; C046410:norhexobarbital; C010226:N-methylcyclobarbital; D006591:Hexobarbital