Krooth R S, Hsiao W L, Lam G F
J Pharmacol Exp Ther. 1978 Nov;207(2):504-14.
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.
尿嘧啶以及或许其他天然嘧啶可能会影响哺乳动物大脑的兴奋水平，原因如下：1）类似于尿嘧啶的六元杂环构成了许多催眠药结构的一部分；2）6-氮尿嘧啶（及其核苷）已被证明对包括人类在内的多种哺乳动物具有催眠作用。给成年雄性C-57小鼠腹腔注射尿苷、6-氮尿苷、胞苷或胸苷会抑制其自发活动。6-氮尿苷的效力远低于所测试的其他核苷。胞嘧啶、巴比妥酸、2-硫代巴比妥酸、2,4-二羟基吡啶以及多种嘧啶分解代谢产物对活动没有影响。胸腺嘧啶、尿嘧啶、6-氮尿嘧啶、巴比妥和苯巴比妥在较低剂量时会增加活动，而在较高剂量时会降低活动。6-氮尿嘧啶和尿嘧啶作为活动刺激剂的效力大致相当，但6-氮尿嘧啶作为活动抑制剂的效力约为尿嘧啶的两倍。比尿嘧啶活性更高的胸腺嘧啶，作为活动刺激剂和抑制剂的效力约为巴比妥的10%。对于胸腺嘧啶和两种巴比妥类药物，ED50（导致活动抑制）与LD50的大小相同，而引起50%活动刺激的剂量比LD50小约一个数量级。这些结果表明，巴比妥类药物可能通过在某些受体处模拟胸腺嘧啶或尿嘧啶的结构来影响兴奋。
