Effects of natural pyrimidines and of certain related compounds on the spontaneous activity of the mouse.

Uracil and perhaps other natural pyrimidines may effect the level of arousal of the mammalian brain since: 1) heterocyclic 6-membered rings, which resemble uracil, form part of the structure of many hypnotics; and 2) 6-azauracil (and its riboside) have shown to be hypnotic for several mammalian species, including man. The parenteral administration of uridine, 6-azauridine, cytidine or thymidine depressed the spontaneous activity of adult male C-57 mice. 6-Azauridine was much less potent than the other ribosides tested. Cytosine, barbituric acid, 2-thiobarbituric acid, 2,4-dihydroxypyridine and a variety of pyrimidine catabolites had no effect on activity. Thymine, uracil, 6-azauracil, barbital and phenobarbital increased activity at lower doses and decreased activity at higher ones. 6-Azauracil and uracil were about equally potent as stimulants of activity, but 6-azauracil had about twice the potency of uracil as a depressant of activity. Thymine, which was more active than uracil, had about 10% the potency of barbital, both as a stimulant and as a depressant of activity. For thymine and the two barbiturates the ED50 (for depression of activity) was of the same magnitude as the LD50, while the dose which caused 50% stimulation of activity was about an order of magnitude less than the LD50. These results suggest that the barbiturates might affect arousal by simulating the structure of thymine or uracil at some receptor.