A novel methylthio metabolite of s-triazolo[3,4-a]phthalazine, a lead compound for the development of antianxiety drugs, in rats.

When s-triazolo[3,4-a]phthalazine (Tri-P) was orally administered in rats, a more lipophilic metabolite M-1 than the parent compound was isolated from the urine. The metabolite M-1 was identified as 7-methylthio Tri-P by means of high resolution MS and two-dimensional NMR spectrometry. Furthermore, the 7-methylthio conjugate was generated from the parent compound Tri-P in isolated rat hepatocytes. Although the contribution of the intestinal microflora to the formation of methylthio metabolite has been pointed out so far, the limited data in this study lead us to conclude that the liver plays a role in all metabolic reactions of Tri-P to its 7-methylthio conjugate in rats.