In Vitro and in Vivo Metabolism of Salsolinol, on Endogenous Isoquinoline Neurotoxin, in Rats

Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, SAL), a dopaminergic isoquinoline neurotoxin, has been implicated to contribute the etiology of Parkinson's disease and neuropathology of chronic alcoholism. In our previous results, SAL was reported to have the mutagenicity and clastogenicity not in bacteria but in mammalian cells, and its genotoxic potential was known to be potentiated in the presence of rat liver S-9 fraction. This may indicate that some metabolite(s) of SAL was involved in the mutagenic potentials. To investigate the SAL metabolites, the metabolism studies of SAL were conducted in vitro rat liver S-9 fraction and in vivo using rats by high performance liquid chromatography and gas chromatography/mass spectrometry. The methylated metabolite of SAL was found in urine of rats, while the same methylating form of metabolite was not produced from the in vitro metabolism system using rat liver S-9 fraction.