Effects of 5-fluorouracil prodrugs on the central nervous system in mice and rats

The effects on the central nervous system (CNS) of mice and rats were determined for the 5-fluorouracil prodrugs, l-(2-tetrahydrofuranyl)-5-fluorouracil (FT), a combination of FT and uracil in a molar ratio of 1:4 (UFT), and l-hexylcarbamoyl-5-fluorouracil (HCFU). Both FT and UFT failed to produce a significant prolongation of hexobarital sleeping time in mice, while HCFU, at the same dose levels, caused a significant (P < 0.01) prolongation of hexo-barbital sleep. FT, UFT, and HCFU produced a slight suppression of coordinating ability in mice, but the effect of HCFU was more pronounced than that of FT and UFT. There were no significant changes in 5-hydroxytryptamine contents in the cerebral cortex and only small insignificant changes of dopamine contents in the corpus striatum by any of the drugs examined. Furthermore, HCFU was more potent than FT and UFT in potentiating the actions of ethanol. These results suggest that HCFU is more toxic to the CNS than are FT and UFT.