Biotransformation of N-methylcyclobarbital in vivo in rabbit and rat

Abstract

1. 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.

2. 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.

3. In the rat, there were almost no differences in the metabolic fates of N-methylcyclobarbital and hexobarbital.

4. 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.