N-Demethylation of Aminopyrine by the Nasal Mucosa in Mice and Rats

Abstract: N-demethylation of aminopyrine was demonstrated in the nasal mucosa of C57 B1 mice and Sprague-Dawley rats by measurements of the ¹⁴CO₂ formed at incubation of ¹⁴C-aminopyrine with tissue-slices. The metabolism of aminopyrine by the nasal mucosa was induced by phenobarbital pretreatment and susceptible to inhibition with metyrapone and SKF 525 A suggesting the presence of a cytochrome P-450-dependent enzyme system in the tissue. Immediately after injection of ¹⁴C-aminopyrine in rats a uniform distribution of radioactivity in the body was recorded. After thirty minutes, however, a preferential localization of radioactivity was found in the nasal mucosa and in the liver. By pretreatment with metyrapone the uptake of radioactivity in the nasal mucosa and in the liver was blocked suggesting that the observed accumulation of radioactivity is due to metabolites.