The fate of dibenz[b,f]-1,4-oxazepine (CR) in the rat. Part II. Metabolism in vitro

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Abstract
1. CR (dibenz[b,f]-1,4-oxazepine) is metabolized by rat liver 105000 g supernatant fractions by (a) ring opening and reduction to 2-amino-2′-hydroxymethyldiphenyl ether and (b) oxidation at C11 to give a cyclic lactam. 2. Reaction (a) is NADPH-dependent, decreased by dialysis and methylene blue, whereas reaction (b) is heat-resistant, inactivated by dialysis, inhibited by CN. p-chloromercuribenzoate, amytal and menadione, and stimulated by methylene blue, phenazine methosulphate and 2,6-dichlorophenol indophenol. Reaction (a) is similar to that of aldehyde reductases (E.C.1.1.1.2) and reaction (b) to that of molybdenum hydroxylases (E.C.1.2.3.1). 3. Reaction (a) is also catalysed by an NADH-dependent enzyme in liver microsomes and subsequent hydroxylation of the lactam also occurs in this cell fraction. 4. Some extrahepatic metabolism of CR occurs via the same routes in kidney, small intestine and lung, though the yield is limited. 5. Digestive gland extract of Helix pomatia converts CR to its lactam in significant amounts. 6. The metabolism of CR in vitro is similar to that predicted from observations in vivo.