Hexobarbital metabolism: a new metabolic pathway to produce 1,5-dimethylbarbituric acid and cyclohexenone-glutathione adduct via 3′-oxohexobarbital

Abstract

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.