Metabolism of peptido-aminobenzophenone (2-o-chlorobenzoyl-4-chloro-N-methyl-N′-glycyl-glycinanilide) in dogs

Abstract

1. The metabolism of a peptido-aminobenzophenone (2-o-chlorobenzoyl-4-chloro-N-methyl-N′-glycyl-glycinanilide) (I) was investigated in dogs after oral administration of 50 mg/kg.

2. Metabolites from urine and plasma extracts were identified by g.l.c., t.l.c., and g.l.c.-mass spectrometry.

3. Metabolites identified in the urine were chlorodiazepam (IV), chlorodesmethyl-diazepam (III), lorazepam (II), and an oxalanilic acid derivative (X). In the plasma. III and IV were detected.

4. The major urinary metabolite was a lorazepam conjugate.

5. A possible main metabolic pathway of I involves formation of the desglycyl compound (XII) via hydrolysis of the terminal amino acid and cyclization to the benzodiazepine type followed by demethylation, 3-hydroxylation and finally conjugation.

6. Formation of the oxanilic acid derivative X from I was a minor route.