Effect of carrageenin treatment on the metabolism of benzydamine and its N-oxide in rat organ preparatons.

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The present study was performed to clarify the in vitro metabolism of benzydamine hydrochloride (BZY·HCl) and benzydamine N-oxide hydrogen maleate (BZY-NO maleate) in rat tissues and the livers of several animals, and to examine the effects of carrageenin on the N-oxygenation and N-demethylation of BZY·HCl, as well as on the N-deoxygenation of BZY-NO maleate in rat blood and liver. The results were as follows. 1) BZY·HCl was mainly metabolized by liver microsomal fraction in the presence of an reduced nicotinamide adenine dinucleotide phosphate (NADPH) generating system and in air. 2) The main reactions were N-oxygenation and N-demethylation, and the former proceeded more rapidly than the latter in all animal species except the guinea pig. 3) No effect of carrageenin of the N-oxygenation and N-demethylation of BZY·HCl was found on comparing liver preparations of control and carrageenin-treated rats. 4) The N-deoxygenation of BZY-NO maleate occurred to the extent of only a few percent in blood, but was significant in the hemolysate (hemoglobin) of erythrocytes, however, the production of methemoglobin was very slight. 5) On the other hand, carrageenin treatment inhibited the N-deoxygenation of BZY-NO maleate in liver preparations, but not in the hemolysate of erythrocytes. The present results account for our previous observation that the N-oxygenation of BZY·HCl in rats is apparently enhanced in the body by carrageenin treatment. Namely, it is suggested that the phenomenon was ascribable not to stimulation of the N-oxygenation of BZY, but to inhibition of the N-deoxygenation of BZY-NO in the liver. These results are discussed in connection with the anti-inflammatory actions of BZY·HCl.

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