A comparison of effects of some 6-azapyrimidines with and without antimetabolite activity on the central nervous system

The activities of 6-azauridine, 6-azauracil, some of 5-alkyl derivatives of 6-azauracil and 1-phenyl derivatives of 6-azauracil in producing a neurological impairment (estimated by dropping off a reversed wire mesh) and behavioural changes (measured on the intensity of exploratory activity) were compared in mice.

The substitution by an alkyl group on C-5 of 6-azauracil, which decrease the antimetabolite activity, increases the intensity and the rapidity of dropping off the mesh parallel to the prolongation of the alkyl chain. On the other hand there was no intensification in depression of exploratory activity with prolongation of alkyl chain. Effective inhibitors of orotidylic acid decar☐ylase—6-azauridine and 6-azauracil—produced depression of exploratory activity in doses ten times lower than those producing dropping off the mesh. Compounds lacking antimetabolite activities—5-alkyl derivatives of 6-azauracil and 1-phenyl derivatives of 6-azauracil—caused the depression of exploratory activity only in doses inducing falling off the mesh suggesting an unspecific character of this effect. In 6-azauridine and 6-azauracil the peak of the falling off the mesh was attained 1 hr after the injection of both substances, while the maximal depression of exploratory activity occurred after 4–5 hr, i.e. at the time when the former effect has already disappeared.

On the basis of this findings it is supposed that the central effects of 6-azauridine and 6-azauracil may be induced both by direct action of their substituted asym-triazine structure (the neurological disturbances) as well as by their specific antimetabolite action (behavioural changes).