The metabolism of a substituted aminoacetamido-benzophenone and cyclization to the corresponding benzodiazepine in the rat in vivo.

1. 2-(5-Cyano-N-methyl-3,5-dimethyl-3-aza-pentanamido)-5-nitrobenzophenone, administered orally to the rat, is well absorbed and extensively metabolized with only minimal quantities of parent compound detected in plasma, bile or urine. 2. Urinary t.l.c. metabolite profiles after oral administration of a substituted aminoacetamidobenzophenone, [14C]C 72 0045, and [14C]nimetazepam were qualitatively similar but differed quantitatively. 3. Analysis by t.l.c. of plasma extracts obtained after oral administration of [14C]C 72 0045 demonstrated that nimetazepam and nitrazepam accounted for 20% of the plasma total radioactivity. Nimetazepam and nitrazepam had a combined concentration up to 22 times greater than the concentration of C 72 0045. 4. The presence of nimetazepam in plasma after oral administration of C 72 0045 was confirmed by mass spectrometry. 5. In the liver, [14C]C 72 0045 was rapidly metabolized to polar metabolites. In the same rats, the major brain metabolites were nimetazepam and nitrazepam. 6. It is concluded that [14C]C 72 0045 undergoes metabolic cyclization in the rat to form nimetazepam, which is further metabolized to form nitrazepam.