Metabolism of afloqualone, a new centrally acting muscle relaxant, in the rat.

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Abstract
The metabolism of afloqualone (6-amino-2-fluoromethyl-3-(o-tolyl)-4(3H)-quinazolinone, AFQ) was studied in rats. AFQ was extensively metabolized by rats after oral administration of 3H-AFQ. Thirteen unconjugated and 3 conjugated metabolites were isolated from the 24-h urine. Their chemical structures were identified or characterized by IR, NMR and mass spectrometry in comparison with synthetic samples. One of the major metabolic pathways of AFQ was acetylation at the 6-amino group followed by hydroxylation of the methyl carbons of the acetyl and 2''-methyl groups. Another important metabolic pathway was the formation of S-containing metabolites in which the F atom at the 2-position of AFQ is replaced by a methylsulfinyl or methylsulfonyl group. These metabolites may be formed via the mercapturic acid conjugate(s) of AFQ. Five metabolites were detected in plasma 1 h after oral administration. They were the N-acetylated and hydroxylated metabolites; the S-containing metabolites found in the urine were not detected in plasma.