Hexobarbital metabolism: a new metabolic pathway to produce 1,5-dimethylbarbituric acid and cyclohexenone-glutathione adduct via 3'-oxohexobarbital.
1. In the presence of glutathione under physiological conditions, 3'-oxohexobarbital was non-enzymically converted to 1,5-dimethylbarbituric acid and a cyclohexenone-glutathione adduct. 2. The two reaction products were characterized by mass spectrometry, 1H- and 13C-n.m.r. spectrometry, and UV spectral analyses. 3. 1,5-Dimethylbarbituric acid was excreted in urine of rat given hexobarbital, 3'-oxohexobarbital, or 1',2'-epoxyhexobarbital, and accounted for 13.4, 14.5 and 4.7% of dose, respectively. 4. The cyclohexenone-glutathione adduct, a novel metabolite of hexobarbital, was excreted in the bile of rat given hexobarbital. 5. The route of 1,5-dimethylbarbituric acid formation via 3'-oxohexobarbital in the metabolism of hexobarbital was discussed in comparison with the epoxide-diol pathway.
Takenoshita
R
R
Faculty of Pharmaceutical Sciences, Fukuoka University, Japan.
Nakamura
T
T
Toki
S
S
D000818:Animals; D001463:Barbiturates / Q000378:metabolism*; D001646:Bile / Q000378:metabolism; D003512:Cyclohexanones / Q000737:chemistry / Q000378:metabolism*; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism*; D006591:Hexobarbital / Q000031:analogs & derivatives* / Q000378:metabolism*; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar
D001463:Barbiturates; D003512:Cyclohexanones; C038084:3'-ketohexobarbital; C036468:cyclohexanone; C038083:1,5-dimethylbarbituric acid; D006591:Hexobarbital; D005978:Glutathione